• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.31-37
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• 2020

We previously identified a new heparinase inhibitor fungal metabolite, named CRM646-A, which showed inhibition of heparinase and telomerase activities in an in vitro enzyme assay and antimetastatic activity in a cell-based assay. In this study, we elucidated the mechanism by which CRM646-A rapidly induced nucleus condensation, plasma membrane disruption and morphological changes by increasing intracellular Ca²⁺ levels. Furthermore, PD98059, a mitogen-activated protein kinase (MEK) inhibitor, inhibited CRM646-A-induced nucleus condensation through ERK1/2 activation in rat 3Y1 fibroblast cells. We identified CRM646-A as a Ca²⁺ ionophore-like agent with a distinctly different chemical structure from that of previously reported Ca²⁺ ionophores. These results indicate that CRM646-A has the potential to be used as a new and effective antimetastatic drug.

• Bulletin of the Korean Chemical Society
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• v.31 no.11
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• pp.3327-3332
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• 2010

We investigated the effects of newly synthesized 4-[(butylsulfinyl)methyl]-1,2-benzenediol (SMBD) on the prevention of atherosclerosis in hypercholesterolemic rabbits. SMBD exhibited stronger inhibition of $Cu^{2+}$-induced low-density lipoprotein oxidation than that of ascorbic acid or simvastatin. Three-month-old rabbits were fed an atherogenic diet containing 0.5% cholesterol and 10% coconut oil, while other two groups were given an atherogenic diet with intravenous injection of either simvastatin or SMBD (0.33 mg/kg/day) for 4 weeks. The concentrations of plasma cholesterol and thiobarbituric acid reactive substances were significantly decreased in SMBD groups, compared to the control group. Also, aortic lipid level in the SMBD group significantly lower than that in the control group. Furthermore, compared with the control group, the SMBD group significantly inhibited the increase of aortic intimal thickness by 36% via reducing of aortic reactive oxygen species and cyclooxygenase-2 protein levels. We conclude that raised antioxidant effect of SMBD results in significant prevention against hypercholesterolemia.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.1-8
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• 2001

Hyperpolarization of arterial smooth muscle by acetylcholine is considered to be produced by the release of an unidentified chemical substance, an endothelium-derived hyperpolarizing factor (EDHF). Several chemicals have been proposed as the candidate for EDHF. However, none of them fulfil completely the nature and property of EDHF. Ultrastructural observation with electron microscope reveals that in some arteries, gap junctions are formed between endothelial and smooth muscle cells. In small arterioles, injection of gap junction permeable dyes into an endothelial cell results in a distribution of the dye to surrounding cells including smooth muscle cells. These observations allow the speculation that myoendothelial gap junctions may have a functional significance. Simultaneous measurement of the electrical responses in both endothelial and smooth muscle cells using the double patch clamp method demonstrates that these two cell types are indeed electrically coupled, indicating that they behave as a functional syncytium. The EDHF-induced hyperpolarization is produced by an activation of $Ca^{2+}-sensitive\;K^+-channels$ that are inhibited by charybdotoxin and apamin. Agonists that release EDHF increase $[Ca^{2+}]_i$ in endothelial cells but not in smooth muscle cells. Inhibition of gap junctions with chemical agents abolishes the agonist-induced hyperpolarization in smooth muscle cells but not in endothelial cells. All these observations can be explained if EDHF is an electrotonic signal propagating from endothelium to smooth muscle cells through gap junctions.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.327-332
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• 2015

Primary cilia have critical roles in coordinating multiple cellular signaling pathways. Dysregulation of primary cilia is implicated in various ciliopathies. To identify specific regulators of autophagy, we screened chemical libraries and identified mefloquine, an anti-malaria medicine, as a potent regulator of primary cilia in human retinal pigmented epithelial (RPE) cells. Not only ciliated cells but also primary cilium length was increased in mefloquine-treated RPE cells. Treatment with mefloquine strongly induced the elongation of primary cilia by blocking disassembly of primary cilium. In addition, we found that autophagy was increased in mefloquine-treated cells by enhancing autophagic flux. Both chemical and genetic inhibition of autophagy suppressed ciliogenesis in mefloquine-treated RPE cells. Taken together, these results suggest that autophagy induced by mefloquine positively regulates the elongation of primary cilia in RPE cells.

• Molecules and Cells
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• v.41 no.12
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• pp.1052-1060
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• 2018

Triclosan (TCS) is a phenolic antimicrobial chemical used in consumer products and medical devices. Evidence from in vitro and in vivo animal studies has linked TCS to numerous health problems, including allergic, cardiovascular, and neurodegenerative disease. Using Caenorhabditis elegans as a model system, we here show that short-term TCS treatment ($LC_{50}$: ~0.2 mM) significantly induced mortality in a dose-dependent manner. Notably, TCS-induced mortality was dramatically suppressed by co-treatment with non-ionic surfactants (NISs: e.g., Tween 20, Tween 80, NP-40, and Triton X-100), but not with anionic surfactants (e.g., sodium dodecyl sulfate). To identify the range of compounds susceptible to NIS inhibition, other structurally related chemical compounds were also examined. Of the compounds tested, only the toxicity of phenolic compounds (bisphenol A and benzyl 4-hydroxybenzoic acid) was significantly abrogated by NISs. Mechanistic analyses using TCS revealed that NISs appear to interfere with TCS-mediated mortality by micellar solubilization. Once internalized, the TCS-micelle complex is inefficiently exported in worms lacking PMP-3 (encoding an ATP-binding cassette (ABC) transporter) transmembrane protein, resulting in overt toxicity. Since many EDCs and surfactants are extensively used in commercial products, findings from this study provide valuable insights to devise safer pharmaceutical and nutritional preparations.

• Journal of the Korean Society of Food Culture
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• v.24 no.6
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• pp.749-755
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• 2009

We investigated the chemical components of red onion powder dried using the low temperature vacuum method and the inhibitory effects of solvent extracts of the dried red onion powder on the growth of HT-1080 human fibrosarcoma and HT-29 human colon cancer cells and $H_2O_2$-induced oxidative stress. The moisture content of the dried red onion powder was 17.95%, while the vitamin C content was 96 mg/100 g and the total phenols content was 39.1 mg/mL. The inhibitory effects of acetone with methylene chloride (A+M) and methanol (MeOH) extracts of the red onion powder on the growth of HT-1080 and HT-29 cancer cells increased in a dose dependent manner (p<0.05). The inhibitory effect was greater on the growth of HT-29 cells, while the A+M extracts had a higher inhibitory effect than the MeOH extracts. Treatment with the hexane, 85% aq. methanol, butanol and water fractions of the extract led to significant inhibition of the growth of both cancer cell lines (p<0.05). Among the fractions, the hexane and 85% aq. methanol fractions showed a greater inhibitory effect. To determine the protective effect on $H_2O_2$-induced oxidative stress, a DCFH-DA (dichlorodihydrofluorescin diacetate) assay was conducted. All fractions, including the crude extracts of dried red onion, appeared to lead to a significant reduction in the levels of intracellular reactive oxygen species (ROS), and these reductions occurred in a dose dependent fashion (p<0.05). Among the fractions, the 85% methanol fraction showed the greatest protective effect on the production of lipid peroxides.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1530-1537
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• 2006

Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health bensfits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum AEPG) on the cell growth of human lung adenocarcinoma NCI-H460 cells in order to understand its anti-proliferative mechanism. AEPG treatment down-regulated the cyclin D1 expression in both transcriptional and translational levels without alteration of cyclin E. In AEPG-treated cells, the levels of cyclin-dependent kinase (C아) 6 mRNA and protein were significantly inhibited, but the levels of Cdk2 and Cdk4 were slightly inhibited by treatment of AEPG. AEPG treatment induced a marked accumulation of Cdk inhibitors, p16 and p27. However, AEPG treatment did not affect not only retinoblastoma protein (pRB) but also tumor suppressor p53 protein expression. The present results indicated that AEPG-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1 phase progression through induction of Cdk inhibitors such as p16 and p27, and inhibition of cyclin D1 and Cdk6. AEPG exposure, as offered by this study, provides cluse for the mechanism of AEPG action. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention and treatiment against human lung cancer.

• Environmental Engineering Research
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• v.25 no.4
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• pp.614-621
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• 2020

Antibiotic pollution is one of the factors contributing to the spread of antibiotic-resistant bacteria in the environment. Advanced oxidation and irradiation processes have been introduced to eliminate antibiotics from water and wastewater. However, few studies have reported the toxic effects of residual antibiotics and their byproducts induced by a treatment system. In this study, we compared the efficacies of chemical (high-performance liquid chromatography (HPLC)) and biological (antimicrobial susceptibility test) assays for measuring the concentrations of residual antibiotics after gamma irradiation for degrading amoxicillin, cephradine, lincomycin, and tetracycline. The concentrations of residual antibiotics estimated using the two assay methods were almost identical, except cephradine. In the case of cephradine, inhibited bacterial growth was observed that was equivalent to twice the concentration measured by HPLC in the samples subjected to gamma irradiation. The observed inhibition of bacterial growth suggested the generation of potentially toxic intermediates following antibiotic degradation. These results indicate that biological and chemical assays should be used in concert for monitoring antibiotic contamination and the toxic derivatives of antibiotic degradation. The results demonstrate that these four antibiotics can be decomposed by 2.0 kGy gamma-irradiation without toxic effects of their byproducts.

• YAKHAK HOEJI
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• v.33 no.3
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• pp.167-174
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• 1989

KR-1008 and KR-30006 are 1,4-dihydropyridine derivatives, new vasodilatory calcium antagonists from KRICT. Calcium antagonistic properties of the compounds were studied in the isolated heart (Langendorff preparation), pulmonary artery (vasodilation), and in the papillary muscle (negative inotropic effect) of the guinea pig. Antihypertensive effect were also investigated after i.v. or oral administration in the SHR (spontaneously hypertensive rat). They produced a sigificant inhibition of Ca-induced contraction in the guinea pig pulmonary artery at the concentrations of above $10^{-8}M$. The negative inotropic effect of the electrically stimulated papillary muscle appeared from the concentration of $10^{-6}M$, which is about hundred times higer than the concentration of vasodilation effect. Left ventricular pressure also decreased from the concentration of $3\;{\times}\;10^{-6}M$ in KR-1008 and KR-3006 in the Langendorff heart preparations. Coronary flow rate increased from $10^{-6}M$ in KR-1008 and nicardipine and appeared no change in KR-30006. The antihypertensive effect of KR-1008 (EC 20: $2.9\;{\mu}g/kg$) was potent more than nicardipine (EC 20: $3.4\;{\mu}g/kg$) and than Kr-30006 (EC 20: $6.8\;{\mu}g/kg$) was, after i.v. bolus injection in the anesthetized SHR. The antihypertensive effect in the conscious SHR appeared 30 minutes after oral administration of 10 mg/kg and persisted 4 hrs in KR-1008 and 12 hrs in KR-30006. Heart rate tended to increase for 0.5-1 hr after oral administration of the test compounds.

• Journal of the Korean Electrochemical Society
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• v.25 no.2
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• pp.51-68
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• 2022

Although lithium metal batteries have a high energy density, experimental skills capable of solving lots of problems induced by dendrite such as short circuit, low coulomb efficiency, capacity loss, and cycle performance are still only in academic research stage. In this paper, research cases for dendrite growth inhibition on lithium metal electrode were classified into four types: flexible SEI (solid electrolyte interface) layer responding to volume expansion of lithium metal electrode, SEI supporting layer to inhibit dendrite growth physically, SHES (self-healing electrostatic shield) mechanism to adjust lithium growth by leading uniform diffusion of Li⁺ ions, and finally micro-patterning to induce uniform deposition of lithium. We hope to advance the practical use of lithium metal electrode by analyzing pros and cons of this classification.