• Journal of Nutrition and Health
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• v.47 no.6
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• pp.394-402
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• 2014

Purpose: Dendropanax morifera Leveille (DML) exhibits diverse biological and pharmacological activities, including anti-oxidative effect, anti-cancer activity, hepatoprotection, immunological stimulation, and bone regeneration. As part of the identification for novel functions of DML, we investigated the therapeutic effects of DML on diabetes induced by streptozotocine (STZ) treatment. Methods: First, the four extracts including the water extract of leaf (DLW), the ethanol extract of leaf (DLE), the water extract of stem (DSW), and the ethanol extract of stem (DSE) were collected from the leaf and stem of DML using a hot water and ethanol solvent. Alterations in body weight, glucose concentration, insulin level, and pancreatic islet structure were investigated in diabetic mice after treatment with extracts of DML for 2 weeks. Results: Among four extracts, the highest level of total polyphenols and total flavonoids was detected in DLW, while the lowest level of these was measured in DSE. The radical scavenging activity was also higher in DLW than in the other three extracts at the concentration of $25-100{\mu}g/mL$, although this activity was maintained at a constant level in all groups at the concentration of $500{\mu}g/mL$. Based on the results of anti-oxidant activity, DLW and DLE were selected for examination of anti-diabetic effects in a diabetes model. Body weight was gradually decreased in all STZ treated groups compared with the No treated group. However, four STZ/DML treated groups maintained a high level of body weight during 7-14 days, while the STZ/vehicle treated group showed a gradual decrease of body weight during the same period. Also, a significant decrease or increase in the concentration of glucose and insulin in the blood of the diabetes model was detected in a subset of groups, although the highest increase was detected in the STZ/DLE-200 treated group. In addition, the histological structure of pancreatic islet was significantly recovered after treatment with DLW and DLE. Conclusion: These results suggest that DLW and DLE may contribute to attenuation of clinical symptoms of diabetes as well as prevent the destruction of pancreatic ${\beta}$-cells in STZ-induced diabetes mice.

• BMB Reports
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• v.38 no.6
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• pp.717-724
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• 2005

The nontoxic B subunit of cholera toxin (CTB) can significantly increase the ability of proteins to induce immunological tolerance after oral administration, when it was conjugated to various proteins. Recombinant CTB offers great potential for treatment of autoimmune disease. Here we firstly investigated the feasibility of silkworm baculovirus expression vector system for the cost-effective production of CTB under the control of a strong polyhedrin promoter. Higher expression was achieved via introducing the partial non-coding and coding sequences (ATAAAT and ATGCCGAAT) of polyhedrin to the 5' end of the native CTB gene, with the maximal accumulation being approximately 54.4 mg/L of hemolymph. The silkworm bioreactor produced this protein vaccine as the glycoslated pentameric form, which retained the GM1-ganglioside binding affinity and the native antigenicity of CTB. Further studies revealed that mixing with silkworm-derived CTB increases the tolerogenic potential of insulin. In the nonconjugated form, an insulin : CTB ratio of 100 : 1 was optimal for the prominent reduction in pancreatic islet inflammation. The data presented here demonstrate that the silkworm bioreactor is an ideal production and delivery system for an oral protein vaccine designed to develop immunological tolerance against autoimmune diabetes and CTB functions as an effective mucosal adjuvant for oral tolerance induction.

• Proceedings of the Korean Vacuum Society Conference
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• 2011.02a
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• pp.1-1
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• 2011

We developed a new generalized synthetic procedure, called as "heat-up process," to produce uniform-sized nanocrystals of many transition metals and oxides without a size selection process. We were able to synthesize uniform magnetite nanocrystals as much as 1 kilogram-scale from the thermolysis of Fe-oleate complex. Clever combination of different nanoscale materials will lead to the development of multifunctional nano-biomedical platforms for simultaneous targeted delivery, fast diagnosis, and efficient therapy. In this presentation, I would like to present some of our group's recent results on the designed fabrication of multifunctional nanostructured materials based on uniform-sized magnetite nanoparticles and their medical applications. Uniform ultrasmall iron oxide nanoparticles of <3 nm were synthesized by thermal decomposition of iron-oleate complex in the presence of oleyl alcohol. These ultrasmall iron oxide nanoparticles exhibited good T1 contrast effect. In in vivo T1 weighted blood pool magnetic resonance imaging (MRI), iron oxide nanoparticles showed longer circulation time than commercial gadolinium complex, enabling high resolution imaging. We used 80 nm-sized ferrimagnetic iron oxide nanocrystals for T2 MRI contrast agent for tracking transplanted pancreatic islet cells and single-cell MR imaging. We reported on the fabrication of monodisperse magnetite nanoparticles immobilized with uniform pore-sized mesoporous silica spheres for simultaneous MRI, fluorescence imaging, and drug delivery. We synthesized hollow magnetite nanocapsules and used them for both the MRI contrast agent and magnetic guided drug delivery vehicle.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.5
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• pp.632-637
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• 2005

This study has been carried out to understand the effect of Hovenia dulcis on the hyperglycemic mice induced with streptozotocin (STZ). Mice in control group were administered with $0.9\%$ saline (2 mL/kg), and experimental groups were administered Hovenia dulcis extract (H1 group, 0.01 g/kg: H2 group, 0.04 g/kg) after hyperglycemic state was induced. Blood glucose concentrations of tile H1 and H2 groups administered with Hovenia dulcis extract for 6 weeks were significantly (p<0.01), compared to control group. Blood glucose tolerance was more favorable in H1 and H2 groups than control group. The Langerhan's islet of pancreas was destructed by treatment of STZ in the control group, but pancreatic islet of the experimental groups was partially recovered from damage, and a number of insulin-positive cells were observed. A number of insulin-like growth factor- I and II (IGF-I and IGF-II) positive cells occurred in the acinar cells of H1 and H2 groups. These results suggest that administration of Hovenia dulcis extract help mice recover from the damage induced with STZ.

• Journal of Yeungnam Medical Science
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• v.11 no.2
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• pp.363-374
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• 1994

The purpose of this study was to investigate the characteristics or the potassium channels existing in the rat urinary bladders. Smooth muscle strips of rat detrusor urinae were examined by isometric myography. Relaxation responses of detrusor muscle strips to the three potassium channel openers pinacidil, a cyanoguanidine derivative, BRL 38227, a benzopyran derivative and RP 52891, a tertrahydrothiopyran derivative were examined. The potassium channel openers reduced the basal tone, and the rank order of potency was RP 52891>pincidil>BRL 38227. Procaine, an inhibitor of the voltage-sensitive potassium channel tended to increase the basal tone, but it did not affect the relaxant effects of the calcium-activated potassium channel opener did not antagonize the relaxant effects, but it reduced the Emax of RP 52891 and BRL 38227. Glibenclamide, an inhibitor of the ATP-sensitive potassium channel, antagonized the relaxant effects of pinacidil, RP 52891 and BRL 38227 reducing the Emax of RP 52891 and BRl 38227. Galanin which inhibits secretion of insulin through opening the ATP-sensitive potassium channels in pancreatic ${\beta}$-cells rather increased the basal tone of the isolated detrusor strips. These results suggest that the urinary bladder of the rat has mainly the ATP-sensitive, glibenclamide sensitive potassium channel, which is a different type from that in the pancreatic ${\beta}$-islet cells..

• Journal of Life Science
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• v.16 no.5
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• pp.767-772
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• 2006

This study was to investigate the effect of betaine on the hypoglycemia and hepatoprotection of streptozotocin(STZ)-induced diabetic rats. Male Sprague-Dawley rats weighing around 280 g were randomly assigned to the three experimental groups: a healthy normal group and two groups with STZ-induced diabetes and fed either control diet or betaine diet. Betaine given to the STZ-diabetic rats had significant effect in lowering the serum glucose concentrations compared to the STZ-diabetic rats. The alanine aminotransferase (AST) and aspartate aminotransferase (ALT) activities and triglyceride contents in serum were dramatically higher in the STZ-diabetic rats, but these increases in relation to diabetes also decreased in the STZ-diabetic rats fed betaine. However, the total-cholesterol concentration in the STZ-diabetic rats was even increased by betaine. The morphology of the pancreatic islets in the normal rats showed a typical round form, but most of the islets in the STZ-diabetic rats showed severe morphological alterations by being markedly destroyed. However, the islet morphology of STZ-diabetic rats given betaine mostly maintained a normal rounded appearance. The present study strongly suggests that the administration of betaine showed a moderate hypoglycemic effect by protecting the pancreatic beta-cells by morphological examination from STZ-induced destruction.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.477-483
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• 2023

The flowers of Carthamus tinctorius (Safflower) were extracted with 80% aqueous methanol (CTex) and the concentrates were partitioned into EtOAc (CTE), n-BuOH (CTB), and H₂O (CTW) fractions. Repeated silica gel (SiO₂) and octadecyl silica gel column chromatographies for the EtOAc and n-BuOH fractions led to isolation of four flavonol glycosides. Nuclear magnetic resornance, infrarad spectroscopy, and mass spectroscopy revealed the chemical structure of the isolated compounds, astragalin (1), isoquercetin (2), nicotiflorin (3), and rutin (4). Quantitative analysis of four isolated compounds in CTex was performed by HPLC. CTex was found to contain 1 at 0.107, 2 at 0.367, 3 at 6.752, and 4 at 0.991 mg/g, respectively. Through this study, an experiment was conducted to evaluate the protective effect on pancreatic islets of the extract, solvent fractions, and all isolated compounds using a zebrafish larvae damaged by alloxan. Pancreatic islet size treated with EtOAc (CTE), n-BuOH (CTB), and H₂O (CTW) fractions and compounds 1-4 significantly increased compared to the alloxan-induced group. These results indicate that C. tinctorius flowers and its isolated compounds are used as potential anti-diabetic agents.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.60-60
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• 2003

Embryonic stem (ES) cells have property of self-renewal and can differentiate into the cells of all three primary germ layers. Recently, many growth factors, alteration of culture condition and gene modifications have been used to differentiate mouse and human ES cells into specific cell types. This study was performed to evaluate the differentiation protocol for human ES cells to the endodermal lineage cells. Human ES cells (Miz-hESl ) were cultured on STO feeder layer mitotically inactivated with mitemycin C, and embryoid bodies (EBs) were formed by suspension culture. Differentiation protocol of EBs consisted of three steps: stage I, culture of EBs for 6 days with ITSFn medium; stage II, culture of stage I cells for 8 days with N2 medium ; stage III, culture of stage II cells for 22 days with N2 medium. mRNA levels of the endodermal lineage differentiation genes were analyzed by semi- quantitative RT-PCR. The Oct-4 expression, a marker of the pluripotent state, was detected in undifferentiated human ES cells but progressively decreased after EBs formation. Differentiating human ES cells expressed marker genes of endodermal differentiation and pancreatic islet cells. GATA4, a-fetoprotein, Glut-2, and Ngn3 were expressed in all stages. However, albumin and insulin were expressed in only stage III cells. The human ES cells can be differentiated into endodermal lineage cells by multiple step culture system using various supplements. We are developing the more effective protocols for guided differentiation of human ES cells.

• BMB Reports
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• v.42 no.10
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• pp.685-690
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• 2009

Angiogenesis is essential for tumor growth and vascular endothelial cell growth factor (VEGF) plays a key role in this process. Conversely, sphingosine 1-phosphate (S1P) is a biologically active sphingolipid known to play a key role in cancer progression by regulating endothelial cell proliferation and migration. In this study, the authors found that S1P increases the level of VEGF mRNA in human umbilical vein endothelial cells (HUVECs) and immortalized HUVECs (iHUVECs). Additionally, S1P was found to increase VEGF promoter activity in MS-1 mouse pancreatic islet endothelial cells. Furthermore, a pharmacological inhibitory study revealed that $G_{\alpha i/o}$-mediated phospholipase C, Akt, Erk, and p38 MAPK signaling are involved in this S1P-induced expression of VEGF. A component of AP1 transcription factor is important for S1P-induced VEGF expression. Taken together, these findings suggest that S1P enhances endothelial cell proliferation and migrat ion by upregulating the expression of VEGF mRNA.

• Clinical and Experimental Pediatrics
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• v.61 no.7
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• pp.217-220
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• 2018

Purpose: Type 1 diabetes mellitus (T1DM) is a chronic and immune-mediated disease, which is characterized by the progressive destruction of pancreatic beta cells. T1DM precipitates in genetically susceptible individuals through environmental factors. In this study, we aimed to evaluate the impact of autoimmunity and intestinal colonization of Candida albicans on the development of T1DM. Methods: Forty-two patients newly diagnosed with T1DM and 42 healthy subjects were included in this monocentric study. The basic and clinical characteristics of the patients were recorded. T1DM-, thyroid-, and celiac-associated antibodies were evaluated. Stool cultures for C. albicans were performed to assess whether or not gut integrity was impaired in patients with T1DM. Results: The evaluation of T1DM- and thyroid-associated antibodies showed that the prevalences of islet cell antibodies and antithyroperoxidase positivity were higher in the study patients than in the patients in the control group. Furthermore, the direct examination and culture of fresh stool samples revealed that 50% of the patients with T1DM and 23.8% of the control subjects had fungi (C. albicans). Conclusion: Through this study, we suggest that the presence of intestinal C. albicans colonization at the time of the diagnosis of T1DM may indicate impairment of normal intestinal microbiota. We also suggest that there may be a tendency of T1DM in patients with a high prevalence of intestinal C. albicans.