• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.308-314
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• 2017

Urotensin II (UII) is a mitogenic and hypertrophic agent that can induce the proliferation of vascular cells. UII inhibition has been considered as beneficial strategy for atherosclerosis and restenosis. However, currently there is no therapeutics clinically available for atherosclerosis or restenosis. In this study, we evaluated the effects of a newly synthesized UII receptor (UT) antagonist, KR-36996, on the proliferation of SMCs in vitro and neointima formation in vivo in comparison with GSK-1440115, a known potent UT antagonist. In primary human aortic SMCs (HASMCs), UII (50 nM) induced proliferation was significantly inhibited by KR-36996 at 1, 10, and 100 nM which showed greater potency ($IC_{50}$: 3.5 nM) than GSK-1440115 ($IC_{50}$: 82.3 nM). UII-induced proliferation of HASMC cells was inhibited by U0126, an ERK1/2 inhibitor, but not by SP600125 (inhibitor of JNK) or SB202190 (inhibitor of p38 MAPK). UII increased the phosphorylation level of ERK1/2. Such increase was significantly inhibited by KR-36996. UII-induced proliferation was also inhibited by trolox, a scavenger for reactive oxygen species (ROS). UII-induced ROS generation was also decreased by KR-36996 treatment. In a carotid artery ligation mouse model, intimal thickening was dramatically suppressed by oral treatment with KR-36996 (30 mg/kg) which showed better efficacy than GSK-1440115. These results suggest that KR-36996 is a better candidate than GSK-1440115 in preventing vascular proliferation in the pathogenesis of atherosclerosis and restenosis.

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.98-103
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• 2020

Marfan syndrome (MFS), a connective tissue disorder caused by mutations in the fibrillin-1 (Fbn1) gene, has vascular manifestations including aortic aneurysm, dissection, and rupture. Its vascular pathogenesis is assumed to be attributed to increased transforming growth factor β (TGFβ) signaling and blockade of excessive TGFβ signaling has been thought to prevent dissection and aneurysm formation. Here, we investigated whether galunisertib, a potent small-molecule inhibitor of TGFβ receptor I (TβRI), attenuates aneurysmal disease in a murine model of MFS (Fbn1^C1039G/+) and compared the impact of galuninsertib on the MFS-related vascular pathogenesis with that of losartan, a prophylactic agent routinely used for patients with MFS. Fbn1^C1039G/+ mice were administered galunisertib or losartan for 8 weeks, and their ascending aortas were assessed for histopathological changes and phosphorylation of Smad2 and extracellular signal-regulated kinase 1/2 (Erk1/2). Mice treated with galunisertib or losartan barely exhibited phosphorylated Smad2, suggesting that both drugs effectively blocked overactivated canonical TGFβ signaling in Fbn1^C1039G/+ mice. However, galunisertib treatment did not attenuate disrupted medial wall architecture and only partially decreased Erk1/2 phosphorylation, whereas losartan significantly inhibited MFS-associated aortopathy and markedly decreased Erk1/2 phosphorylation in Fbn1^C1039G/+ mice. These data unexpectedly revealed that galunisertib, a TβRI inhibitor, showed no benefits in aneurysmal disease in MFS mice although it completely blocked Smad2 phosphorylation. The significant losartan-induced inhibition of both aortic vascular pathogenesis and Smad2 phosphorylation implied that canonical TGFβ signaling might not prominently drive aneurysmal diseases in MFS mice.

• Korean Journal of Food Science and Technology
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• v.46 no.5
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• pp.575-580
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• 2014

Model gel food samples of yanggaeng (Y) were prepared for the elderly with various gelling agents, including agar (AG), low acyl gellan (GL), ${\kappa}$-carrageenan (CA), locust bean gum (LB), glucomannan (GM), and xanthan gum (XA) in different combinations as follows (in 1:1 ratio): LB+CA, GM+XA, and GM+CA. The quality characteristics of the different combinations were compared. The results revealed that water loss was highest for Y-GL, whereas there was no significant difference among the other samples. Y-GL showed the highest values for lightness in color, whereas Y-AG showed the lowest. Regarding textural properties, Y-LB+CA had the highest hardness value, whereas Y-GL had the lowest; the hardness of Y was related to the cross-section of the added gel. Finally, Y-GM+XA exhibited the highest score in overall acceptability in the sensory test by elderly, indicating that the preferable texture by elderly is slightly chewy, but not adhesive.

• Journal of Nutrition and Health
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• v.36 no.10
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• pp.1013-1021
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• 2003

Anemia, the condition of the diminished concentration of hemoglobin per erythrocyte is common in patients with cancer and is a frequent complication of myelosuppressive chemotherapy. Cham-Dang-Gui (Angelicae Gigantis Radix) has been used in traditional Korean medicine to treat hematologic deficiencies. In this study, Cyclophosphamide (CYP), an alkylating agent that has a broad spectrum of anti-cancer activities, was intraperitoneally injected into the experimental animals to suppress the bone marrow thereafter, causing anemia. The hemopoietic effects of Cham-Dang-Gui were examined using anemic rat model. Rats were divided into five groups: CON (control group), ANS (CYP-injected + normal diet), AND (CYP-injected + normal diet + Cham-Dang-Gui), ALS (CYP-injected + low iron diet), and ALD (CYP-injected + low iron diet + Cham- Dang-Gui) groups. CYP (30 mg/kg) was intraperitoneally injected to rats for 3 days to induce anemic condition. Saline or Cham-Dang-Gui was administrated orally during the entire experimental period. CYP injection decreased body weight gain and food consumption in comparison with CON group. Oral administration of Cham-Dang-Gui extract with normal iron diet significantly prevented the lower body weight gain. The blood level of hemoglobin, iron status (serum iron, transferrin, ferritin and TIBC) and blood level of vitamin B-12 in Cham-Dang-Gui treated groups were significantly higher than those of Cham-Dang-Gui untreated groups regardless of amount of iron in the diet. Taken together, it could be concluded that the Cham-Dang-Gui extract could improve anemic condition induced by CYP injection by improving hematological value, iron status and vitamin B12 status in rats.

• Nutrition Research and Practice
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• v.7 no.4
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• pp.249-255
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• 2013

In this study, the protective effects of EGCG on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced oxidative cell death in catecholaminergic PC12 cells, the in vitro model of Parkinson's disease, were investigated. Treatment with L-DOPA at concentrations higher than $150{\mu}M$ caused cytotoxicity in PC12 cells, as determined using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry detection. The apoptotic ratio was similar in cells treated with $100{\mu}M$ EGCG plus $150{\mu}M$ L-DOPA (5.02%) and the control (0.96%) (P > 0.05), and was lower than that of cells treated with L-DOPA only (32.24%, P < 0.05). The generation level of ROS (% of control) in cells treated with EGCG plus L-DOPA was lower than that in cells treated with L-DOPA only (123.90% vs 272.32%, P < 0.05). The optical density in production of TBARS in cells treated with L-DOPA only was higher than that in the control ($0.27{\pm}0.05$ vs $0.08{\pm}0.04$, P < 0.05), and in cells treated with EGCG only ($0.14{\pm}0.02$, P < 0.05), and EGCG plus L-DOPA ($0.13{\pm}0.02$, P < 0.05). The intracellular level of GSH in cells treated with EGCG plus L-DOPA was higher than that in cells treated with L-DOPA only ($233.25{\pm}16.44$ vs $119.23{\pm}10.25$, P < 0.05). These results suggest that EGCG protects against L-DOPA-induced oxidative apoptosis in PC12 cells, and might be a potent neuroprotective agent.

• Advances in environmental research
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• v.9 no.2
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• pp.135-150
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• 2020

Many industries, such as textiles, chemical refineries, leather, plastics and paper, use different dyes in various process steps. At the same time, these industrial sectors are responsible for discharging contaminants that are harmful and toxic to humans and microorganisms by introducing synthetic dyes into wastewater. Of these dyes, methylene blue dye, which is classified as basic dyes, is accepted as a model dye. For this reason, methylene blue dye was selected in the study and its removal from the water was studied. In this study, two efficient biosorbents were developed from chitosan and sunflower waste, an agro-industrial waste and modified using iron nanoparticles. The biosorption efficiency was evaluated for methylene blue (MB) dye removal from aqueous solution under various parameters such as treating agent, solution pH, biosorbent dosage, contact time, initial dye concentration and temperature. We investigated the kinetic properties of dye removal from water for Chitosan-Sunflower (CS), Chitosan-Sunflower-Nanoiron (CSN). When the wavelength of MB dye was spectrophotometrically scanned, the maximum absorbance was determined as 660 nm. For the core shell biosorbents we obtained, we found that the optimum time for removal of MB from wastewater was 60 min. The pH of the best pH was determined as 5 in the studied pH. The most suitable temperature for the experiment was determined as 30℃. SEM-EDAX, TEM, XRD, and FTIR techniques were used to characterize biosorbents produced and modified in the experimental stage and to monitor the change of biosorbent after dye removal. The interactions of the paint with the surface used for removal were explained by these techniques. It was calculated that 80% of CS and 88% of CSN removed MB in optimum conditions. Also, the absorption of MB dye onto the surface was investigated by Langmiur and Frendlinch isotherms and it was determined from the results that the removal was more compatible with Langmiur isotherm.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.522-527
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• 2002

The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis shwed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the anti metastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.

• International Journal of Stem Cells
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• v.10 no.1
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• pp.1-11
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• 2017

Human cardiomyocytes (CMs) cease to proliferate and remain terminally differentiated thereafter, when humans reach the mid-20s. Thus, any damages sustained by myocardium tissue are irreversible, and they require medical interventions to regain functionality. To date, new surgical procedures and drugs have been developed, albeit with limited success, to treat various heart diseases including myocardial infarction. Hence, there is a pressing need to develop more effective treatment methods to address the increasing mortality rate of the heart diseases. Functional CMs are not only an important in vitro cellular tool to model various types of heart diseases for drug development, but they are also a promising therapeutic agent for cell therapy. However, the limited proliferative capacity entails difficulties in acquiring functional CMs in the scale that is required for pathological studies and cell therapy development. Stem cells, human pluripotent stem cells (hPSCs) in particular, have been considered as an unlimited cellular source for providing functional CMs for various applications. Notable progress has already been made: the first clinical trials of hPSCs derived CMs (hPSC-CMs) for treating myocardial infarction was approved in 2015, and their potential use in disease modeling and drug discovery is being fully explored. This concise review gives an account of current development of differentiation, purification and maturation techniques for hPSC-CMs, and their application in cell therapy development and pharmaceutical industries will be discussed with the latest experimental evidence.

• Korean Journal of Chemical Engineering
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• v.35 no.12
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• pp.2394-2402
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• 2018

Textile dyes are some of the pollutants which have received the most attention because of the large volume of wastewater generated by the textile industry. Removal by means of adsorption is one of the most versatile alternatives to treat these effluents. Even though different adsorbents such as activated carbons and mineral materials have been proposed, polymeric adsorbents are a viable alternative. This work reports for the first time the use of polyelectrolyte PTZ and macroelectrolyte MTZ containing tetrazole groups as adsorbents useful in the textile dyes removal present in aqueous solutions and wastewater. Because of the anionic character of the tetrazole group, MTZ exhibits selective adsorption capabilities for cationic dyes of up to $156.25mg{\cdot}g^{-1}$. The kinetic study of the process of adsorption shows that PTZ and MTZ fit a pseudo second-order model. MTZ also shows utility as a flocculant agent in the treatment of wastewater containing dyes Indigo Blue and Reactive Black. The results showed that PTZ and MTZ may be used in the treatment of wastewater in a process of coagulation-flocculation followed by the treatment by adsorption. This two-stage treatment removed up to 95% of the dye present in the wastewater. As well as removing the dyes, the values for COD, suspended solids, pH, and color of the wastewater decreased, thus significantly improving its quality.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.401-415
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• 2002

Lim and his coworkers (1987; 1988; 1989) have also found that all of total Ginseng saponin, panaxadiol-and panaxatriol-type saponins cause the increased secretion of catecholamines (CA) in a $Ca^{2+}$ -dependent fashion from the isolated perfused rabbit adrenal glands through the activation of cholinergic (both nicotinic and muscarinic) receptors. These CA secretory effects are partly due to the direct action on the rabbit adrenomedullary chromaffin cells. However, the present study was designed to examine the effect of total ginseng saponin on CA secretion evoked by activation of cholinergic nicotinic receptors in the isolated perfused model of the rat adrenal gland. Total ginseng saponin given (100 ${\mu}g$/20 min) into an adrenal vein did fail to produce alteration of spontaneous CA release from the rat adrenal medulla. Acetylcholine(5.32 mM)- and DMPP(100 ${\mu}M$, a selective nicotinic receptor agonist)-evoked CA secretory responses were reduced markedly after the pretreatment with the total ginseng saponin at a rate of 100 ${\mu}g$/6.2 ml/20 min, respectively. Pretreatment with total ginseng saponin also depressed greatly high potassium (56 mM, a membrane depolarizing agent)- and Bay-K-8644 (10 ${\mu}M$, a calcium channel activator)-induced CA secretions. Taken together, it is thought that total ginseng saponin can inhibit the releasing effect of CA evoked by nicotinic receptor stimulation from the isolated perfused rat adrenal medulla, which seems to be associated to the direct inhibition of influx through L-type calcium channel into the rat adrenomedullary chromaffin cells. It seems that there is species differences in the adrenomedullary catecholamine secretion between the rabbit and rat.