• Molecules and Cells
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• v.43 no.7
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• pp.619-631
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• 2020

In this study, we describe a novel function of TNNC1 (Troponin C1, Slow Skeletal and Cardiac Type), a component of actin-bound troponin, as a tumor suppressor of lung adenocarcinoma (LUAD). First, the expression of TNNC1 was strongly down-regulated in cancer tissues compared to matched normal lung tissues, and down-regulation of TNNC1 was shown to be strongly correlated with increased mortality among LUAD patients. Interestingly, TNNC1 expression was enhanced by suppression of KRAS, and ectopic expression of TNNC1 in turn inhibited KRAS^G12D-mediated anchorage independent growth of NIH3T3 cells. Consistently, activation of KRAS pathway in LUAD patients was shown to be strongly correlated with down-regulation of TNNC1. In addition, ectopic expression of TNNC1 inhibited colony formation of multiple LUAD cell lines and induced DNA damage, cell cycle arrest and ultimately apoptosis. We further examined potential correlations between expression levels of TNNC1 and various clinical parameters and found that low-level expression is significantly associated with invasiveness of the tumor. Indeed, RNA interference-mediated down-regulation of TNNC1 led to significant enhancement of invasiveness in vitro. Collectively, our data indicate that TNNC1 has a novel function as a tumor suppressor and is targeted for down-regulation by KRAS pathway during the carcinogenesis of LUAD.

• Proceedings of the Korean Vacuum Society Conference
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• 2013.02a
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• pp.108-109
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• 2013

Mitochondria play key roles in the production of cell's energy. Their dominant function is the synthesis of adenosine 5'-triphosphate (ATP) from adenosine diphosphate (ADP) and phosphate (Pi) through the oxidative phosphorylation. Evaluation of drug-induced mitochondrial toxicity has become increasingly important since mitochondrial dysfunction has recently been implicated in numerous diseases including cancer and diabetes mellitus. Mitochondrial functions have been monitored via oxygen consumption, mitochondrial membrane potential, and more importantly via ATP synthesis since ATP synthesis is the most essential function of mitochondria. Various analytical methods have been employed to investigate ATP synthesis in mitochondria, including high performance liquid chromatography (HPLC), bioluminescence technique, and pH measurement. However, most of these methods are based on destructive analysis or indirect monitoring through the enzymatic reaction. Infrared absorption spectroscopy (IRAS) is one of the useful techniques for real-time, label-free, and direct monitoring of biological reactions [1,2]. However, the strong water absorption requires very short path length in the order of several micrometers. Transmission measurements with thin path length are not suitable for mitochondrial assays because solution handlings necessary for evaluating mitochondrial toxicity, such as rapid mixing of drugs and oxygen supply, are difficult in such a narrow space. On the other hand, IRAS in the multiple internal reflection (MIR) geometry provides an ideal optical configuration to combine solution handling and aqueous-phase measurement. We have recently reportedon a real-time monitoring of drug-induced necrotic and apoptotic cell death using MIR-IRAS [3,4]. Clear discrimination between viable and damaged cells has been demonstrated, showing a promise as a label-free and real-time detection for cell-based assays. In the present study, we have applied our MIR-IRAS system to mitochondria-based assays by monitoring ATP synthesis in isolated mitochondria from rat livers. Mitochondrial ATP synthesis and hydrolysis were in situ monitored with MIR-IRAS, while dissolved oxygen level and solution pH were simultaneously monitored with O2 and pH electrodes, respectively. It is demonstrated that ATP synthesis and hydrolysis can be monitored by the IR spectral changes in phosphate groups in adenine nucleotides and MIR-IRAS is useful for evaluating time-dependent drug effects of mitochondrial toxicants.

• Food Science of Animal Resources
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• v.33 no.2
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• pp.276-280
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• 2013

Obesity, the leading metabolic disease, is a prevalent health problem in industrialized countries and is closely associated with coronary heart disease, hypertension, diabetes, and even cancer. In this study, we investigated the effects of dip-sauce for meat containing Garcinia cambogia extract (GC) on the lipid accumulation and body weight reduction in rats fed high-fat diet for three months. Eighteen Sprague Dawley male rats of five-week-old were randomly assigned to one of three groups; normal chew diet (NCD) group, high-fat diet plus GC-noncontaining dip-sauce (HFD) group, and HFD plus GC-containing dip-sauce (HFD+GC) group. Co-administration of GC-containing dip-sauce (5 g/kg body weight/day) with HFD significantly attenuated cumulative body weight gain, compared with NCD or HFD groups. Both epididymal and perirenal fat pad weights in the HFD plus GC group were significantly lower than those of HFD or NCD groups. Administration of GC-containing dip-sauce also resulted in significant reduction in the serum levels of total cholesterol, total lipid, and triglyceride, compared with NCD or HFD groups. Thus, GC-containing dip-sauce confers beneficial effects to pathological states associated with metabolic disorder via its anti-obesity and lipid lowering properties.

• Korean Journal of Food Science and Technology
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• v.33 no.6
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• pp.656-663
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• 2001

The most representative nitrosamine derived from nicotine, nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), has been reported to cause lung cancer in A/J mice. It has been also demonstrated that NNK-induced lung tumorigenesis involves $O^6-methylguanine(O^6MeG)$ formation, leading to $GC\;{\rightarrow}\;AT$ transitional mispairing during DNA replication. Our in vitro experiment, modified from the method of DBA assay, examined the ability of phyto-extract mixture to inhibit the metabolism of nicotine to nitrosamines. The production of nitromorpholine from morpholine was inhibited about 75% at the concentration of 20 mg/mL of phyto-extract mixture, which was lower than vitamine C and green tea powder. NNK, which is a pro-carcinogen in laboratory animals, is hydroxylated primarily in liver and lung by CYP 1A2, 2A6 and 3A4. A critical phase. of NNK activation is its change to an unstable metabolite methyl-diazohydroxide via CYP-mediated ${\alpha}-hydroxylation$; and then it provides a methyl group to the DNA to form DNA adducts which can easily induce mutations. $Aroclor^R$ 1254 was used to induce CYPs in the liver of a Sprague-Dawley rat. The ability of various test samples to inhibit CYPs that participate in NNK activation was evaluated, following the removal of the liver from the rat. Microsomal CYPlA2 catalyzing the conversion of NNK into strong carcinogenic chemicals was inhibited more efficiently by phyto-extract mixture than green tea powder. These results indicate that phyto-extract mixture can be used to reduce $O^6MeG$ DNA adducts for chemoprevention.

• Korean Journal of Medicinal Crop Science
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• v.10 no.1
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• pp.41-45
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• 2002

An efficient and reproducible procedure for the large scale propagation of Hovenia dulcis Thunb. is described. Shoot primodia emerging from the leaf surface was induced from MS medium supplemented with NAA. Stem cuttings were suitable explants for multiple shoot proliferation. They produced axillary shoots which branched repeatedly, yielding an average of 7 shoots per explants after 4 weeks in culture, when cultured on a woody plant medium (WPM) containing 0.1mg/l BA and 0.1mg/l NAA. Stem, leaf and root segments from axenic seedlings were used as explant source to induce somatic embryogenesis. A high frequency of somatic embryos were induced directly from leaf in MS medium with NAA, 2,4-D and in medium containing NAA, 2,4-D with BA. Somatic embryos were germinated in MS medium supplemented with 1mg/ l $GA_3$. Somatic embryos proliferated secondary somatic embryos rapidly after transfer to MS medium supplemented with 1mg/ l kinetin, 1mg/ l $GA_3$ and 2% dextrose.

• Korean Journal of Construction Engineering and Management
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• v.14 no.5
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• pp.55-64
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• 2013

The complexity of constructing medical institutions is higher than that of general buildings, and many change orders in the design and defect repairs in the construction phase are required due to strict government regulations. The priority control of constructions and impact factors of medical institutions were analyzed in this study, and difficulties in the control in the design and construction phase were identified. First, the priority management factors that were identified were as follows: architecture, facilities, and electricity. Second, 1) priority management in constructions and factors resulting in change orders and 2) priority management in constructions involving defect repair were analyzed. Third, the importance recognized by the construction managers were analyzed. The priority management in constructions and factors that were recognized by the construction manager were deducted as having low importance, although there were many change orders and defects. The work of finishing, wall building, joining, office automation and communication function, and lighting were analyzed in the design phase, and waste, the office automation and communication function, ceilings, contamination control, and plumbing were analyzed in the construction phase. The results showed that there will be a decrease in change orders and defects if the concentration of the manager was elevated and priorities were managed.

• Herbal Formula Science
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• v.23 no.2
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• pp.199-208
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• 2015

Objectives : In the present study, we investigated the effects of ethanol extract of Scutellaria baicalensis (EESB) on the progression of cell cycle in human renal cell carcinoma Caki-1 cells. Methods : The effects of EESB on cell growth and apoptosis induction were evaluated by trypan blue dye exclusion assay and flow cytometry, respectively. The mRNA and protein levels were determined by Western blot analysis and reverse transcription-polymerase chain reaction, respectively. Results : It was found that EESB treatment on Caki-1 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by Annexin V-FITC staining. The flow cytometric analysis indicated that EESB resulted in G2/M arrest in cell cycle progression which was associated with the down-regulation of cyclin A expression. Our results also revealed that treatment with EESB increased the mRNA and proteins expression of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), without any noticeable changes in cyclin B1, Cdk2 and Cdc2. In addition, the incubation of cells with EESB resulted in a significant increase in the binding of p21 and Cdk2 and Cdc2. These findings suggest that EESB-induced G2/M arrest and apoptosis in Caki-1 cells is mediated through the p53-mediated upregulation of Cdk inhibitor p21. Conclusions : Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent and further studies will be needed to identify the biological active compounds that confer the anti-cancer activity of S. baicalensis.

• The Journal of Korean Medicine
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• v.17 no.1 s.31
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• pp.111-131
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• 1996

For the development of antimetastatic agent 41 kinds of crude drugs were used for the evaluation of inhibitory effect of several crude drugs on cell adhesion of pulmonary cancer cells and platelet aggregation. Results were obtained as follows: 1. Water extracts of crude drugs inhibited cell adhesion of A549 to complex extracelluar matrix over 40 % of contol were Houttuyniae Herba, Mylabris, Rhei Radix et Rhizoma, Meliae Cortex, Ferula Resina, Oldenlandiae diffusae Herba at the higher concentration of $10^{-3}g／ml$ while those inhibiting cell adhesion of Bl6-Fo over 40 % of control were $10^{-5}g／ml$ of Houttuyniae Herba, Aurantii Fructus, Lithospermi Radix, Zedoariae Rhizoma. Prunellae Spica, Foeniculi Fructus, Rbei Radix, Scutellariae Radix, Meliae Cortex, Ferula Resina and Oldenlandiae diffusae Herba. 2. MeOH extracts of crude drugs at the concentration of $4{\times}10^{-4}g／ml$ inhibiting cell adhesion of A549 specifically to single extracelluar matrix over 40 % of control were Lithospermi Radix, Agrimoniae Herba, Rhei Radix and Ferula Resina to collagen I, Houttuyniae Herba, Lithospermi Radix, Bupleuri Radix, Salviae miltiorrhizae Radix, Orostachys Herba, Sappan Lignum, Meliae cortex ferula Resina and Coicis Semen to collagen Ⅳ, Mylabris, Agrimoniae Herba to laminin, Houttuyniae Herba and Meliae Cortex to fibronectin. 3. NeOH extracts of crude drugs at the concentration of $4{\times}10^{-4}g／ml$ inhibiting cell adhesion of B16-Fo specifically to single extracelluar matrix over 60 % of control were Lithospermi Radix, Salviae miltiorrhizae Radix, Meliae Cortex and Ferula Resina to collagen I, Lithospermi Radix, Bupleun Radix, Saiviae miltiorrhizae Radix, Ferula Resina and Acanthopanacis Cortex to collagen Ⅳ, Bupleuri Radix, Orostachys Herba to laminin, Houttuyniae Herba to fibronectin. 4. MeOH extracts of crude drugs inhibiting platelet aggregation over 40% of ADP control were at the concentration of $50{\mu}g/m{\ell}$ of Houttuyniae Herba, Angilicae gigantis Radix, Zedoariae Rhizoma. Coicis Semen and $100{\mu}g/m{\ell}$ of Ferula Resina, Orostachys Herba, Salviae miltiorrhizae Radix, Curcumac Radix, Carthami Flos, Lithospermi Radix, Gleditsiae Spina, Sappan Lignum, Acanthopanacis Cortex. These results suggest that several crude drugs including Ferula Resina, Houttuyniae Herba, Lithospermi Radix and Salviae miltiorrhizae Radix chiefly have more possibility to exert antimetastatic activity and require in vivo antimetastatic study.

• The Journal of Korean Medicine
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• v.17 no.1 s.31
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• pp.266-279
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• 1996

To complement and develop the Orient Medical Bian Zheng treatmemt(韓方辨證施治), I have observed and analysed 68 persons who have recieved medical treatment because of the epigastric pain. Considering and analysed the Clinical Diagnosis(臨床診斷) and Clinical Bian Zheng(臨床辨證), Clinical Diagnosis(臨床診斷) and Gastroscopic Bian Zheng(微觀辨證), Clinical Bian Zheng(臨床辨證) and Gastroscopic Bian Zheng(微觀辨證), case history, age and sex, I have obtained the conclusion as follows. 1. The frequency of epigastric pain according to the classfication of Clinical Bian Zheng(臨床辨證) most occured in Gi Che Zheng(氣滯證), then in Huh Han Zheng(虛寒證). and least in Wi Youl Zheng. 2. There is no clear connection between the Clinical Bian Zheng(臨床辨證) and Clinical Diagnosis(臨床診斷). 3. The frequency of the epigastric pain according to Gastroscopic Bian Zheng(微觀辨證), mainly occurred in Wi youl Type(胃熱型), Wi Rac Jac Sang Type(胃絡灼傷滯型)and then occurred in Wi Han Type(胃寒型), and least occurred in Wi Rac A Che Type(胃絡瘀滯型) 4. Having observed the relation between the Gastroscopicin Bian Zheng(微觀辨證), and Clinical Diagnosis(臨床診斷) as pathological process, I have obtained the result that Wi Youl type(胃熱型) and Wi Rac Jac Sang Type(胃絡灼傷型) mainly occurred in Erosive Gastritis and Superficial Gastritis at the early stage, and Wi Rac A Che Type(胃絡瘀滯型) occurred in the whole stage among the Wuperficial Gastritis, Atro pic Gastritis, and Erosive Gastritis, Gastric Cancer, and the Wi Han Type(胃寒型) mainly occurred in Atropic Gastritis at the later stage. 5. The relation between Clinical Bian Zheng(臨床辨證) and Gastroscopic Bian Zheng(微觀辨證) do not coincide. 6. Observing the relation between the Clinical Bian Zheng(臨床辨證) and case history, Gi Che Zheng(氣滯證), Huh Han Zheng(虛寒證), Wi Youl Zheng(胃熱證) were commonly seen in the early stage of the case history, and Eum Huh Zheng(陰虛證) and Houl A Zheng(血瘀證) were seen in every stage. 7. Observing the relation between the Clinical Bian Zheng(臨床辨證) and age, Gi Che Type(氣滯型) was mostly seen in the thirties and other Bian Zheng(辨證) was seen after the middle 8. Observing the relation between the Clinical Bian Zheng(臨床辨證) and sex, Gi Che Type(氣滯型) was seen at high ratio in both sexes. 9. Observing the relation between the Gastroscopic Bian Zheng(微觀辨證) and case history Wi Han Type(胃寒證), Wi Youl Type(胃熱型), Wi Rac Jac Sang Type(胃絡灼傷型) were seen in the early stage of the case history Wi Rac A Che Type(胃絡瘀滯型) was mostly seen in the later stage. 10. There was no clear connection between the Gastroscopic Bian Zheng(微觀辨證) and age, sex. Although the examples were not sufficient, recipe regarding the partial variation state of stomach mucos together with Orient Medical Bian Zheng(韓方辨證) treatment seems to be useful in the effective treatment of Bi wi(脾胃) disease besides the epigastric pain.

• The Journal of Korean Medicine
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• v.30 no.1
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• pp.51-63
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• 2009

Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.