• BMB Reports
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• v.45 no.3
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• pp.147-152
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• 2012

Methylglyoxal (MG) was identified as an intermediate in non-enzymatic glycation and increased levels were reported in patients with diabetes. In this study, we evaluated the effects of MG on the modification of ferritin. When ferritin was incubated with MG, covalent crosslinking of the protein increased in a time- and MG dose-dependent manner. Reactive oxygen species (ROS) scavengers, $N-acetyl-_L-cysteine$ and thiourea suppressed the MG-mediated ferritin modification. The formation of dityrosine was observed in MG-mediated ferritin aggregates and ROS scavengers inhibited the formation of dityrosine. During the reaction between ferritin and MG, the generation of ROS was increased as a function of incubation time. These results suggest that ROS may play a role in the modification of ferritin by MG. The reaction between ferritin and MG led to the release of iron ions from the protein. Ferritin exposure to MG resulted in a loss of arginine, histidine and lysine residues. It was assumed that oxidative damage to ferritin caused by MG may induce an increase in the iron content in cells, which is deleterious to cells. This mechanism, in part, may provide an explanation or the deterioration of organs under diabetic conditions.

• Food Science of Animal Resources
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• v.34 no.1
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• pp.127-132
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• 2014

Optimization of carnosine and anserine extraction from chicken breast was performed using response surface methodology (RSM) to obtain the maximized physiological activities for anti-glycation and anti-oxidation. The optimum extraction conditions were water extraction for 1.6 h in the case of the 20-wk laying hen muscle and water extraction for 2.12 h in the case of 90-wk laying hen muscle. Higher carnosine and anserine contents were measured in the 20-wk laying hen muscle, along with higher physiological activities, which increased in direct proportion with the dipeptide contents. The extracts prepared from the 20-wk laying hen under optimum conditions showed 57% inhibition of advanced glycated end-product formation, 64% inhibition of lipid peroxidation, and 61% of DPPH radical scavenging effects. On the other hand, 52% inhibition of AGE formation, 62% inhibition of lipid peroxidation, and 53% of DPPH radical scavenging effect were demonstrated within the 90-wk laying hen. In addition, the ratio of carnosine was a key indicator for the physiological activities of the extracts.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.50 no.5
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• pp.481-486
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• 2017

The content of $N^{\varepsilon}$-(carboxymethyl)lysine (CML), an advanced glycation endproduct, in stir-fried anchovy prepared under different cooking conditions was determined, along with their sensory properties. The aim of the study was to optimize cooking conditions of stir-fried anchovy for minimal CML production by using different sugars, sugar concentrations, pH levels, and cooking times. The results showed that CML content increased with increasing sugar concentration. Cooking time did not affect CML content but lowering the pH with lemon juice decreased it significantly. The CML content of samples with a high sugar concentration, and without lemon juice was $4.67{\mu}g/mL$, and that of samples with both a low sugar concentration and lemon juice was $2.49{\mu}g/mL$, indicating a 47% reduction in the CML content of sir-fried anchovy. We conclude that stir-fried anchovy cooked with less sugar and the addition of lemon juice can reduce CML content while maintaining sensory characteristics.

• Korean Journal of Environmental Biology
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• v.28 no.1
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• pp.8-13
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• 2010

This study aimed the role of gold nanoparticles (AuNP) in advanced glycation end-products (AGEs) induced migration and invasion in bovine retinal endothelial cells (BRECs). BRECs were isolated from the retina. Cell viability was confirmed by the MTT assay. In vitro wound migration assay was performed to investigate the migration of BRECs. In vitro tube formation was measured by on-gel system. Apoptosis induced by AuNP was confirmed by caspase-3 assay. AGE-bovine serum albumin (BSA) demonstrated increase of cell migration and proliferation in BRECs. In addition, AuNP regardless of the existence of AGE-BSA suppressed proliferation, migration, and angiogenesis. AuNP suppressed AGE-BSA induced migration and invasion, and induced apoptosis through caspase-3. As a results, AuNP have a potential anti-angiogenic effect for AGE-induced angiogenesis in vitro and offer possibility for the treatment of diabetic retinopathy.

• Natural Product Sciences
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• v.22 no.3
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• pp.175-179
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• 2016

The aim of this study was to evaluate the anti-diabetic effects of the water extract of Lespedeza cuneata (LCW) using rat insulinoma (RIN) m5F cells and streptozotocin (STZ)-induced diabetic rats. The effect of LCW on the protection of pancreatic beta cells was assessed using MTT assay, and nitric oxide production was assessed using Griess reagent. STZ-induced diabetic rats were treated with 100 and 400 mg/kg body weight of LCW for 5 weeks. In results, LCW significantly protected cytokine-induced toxicity and NO production, and increased insulin secretion in RINm5F cells. LCW significantly decreased serum blood glucose, thiobarbituric acid reactive substances (TBARS), blood urea nitrogen (BUN) and advanced glycation end products (AGEs) levels, and renal fibronectin expression in STZ-induced diabetic rats. Also, LCW effectively improved BW loss in STZ-induced diabetic rats. Thus, our results suggest that LCW has a beneficial effect on cytokine-induced pancreatic beta cell damage and biomarkers of diabetic complication in hyperglycemic rats.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.158-164
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• 2017

Methylglyoxal (MGO) is a highly reactive metabolite of glucose which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Hypericin, a naphthodianthrone isolated from Hypericum perforatum L. (St. John's Wort), is a potent and selective inhibitor of protein kinase C and is reported to reduce neuropathic pain. In this work, we investigated the protective effect of hypericin on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Hypericin showed significant anti-apoptotic activity in MGO-treated HUVECs. Pretreatment with hypericin significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. Hypericin prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. MGO was found to activate mitogen-activated protein kinases (MAPKs). Pretreatment with hypericin strongly inhibited the activation of MAPKs, including P38, JNK, and ERK1/2. Interestingly, hypericin also inhibited the formation of AGEs. These findings suggest that hypericin may be an effective regulator of MGO-induced apoptosis. In conclusion, hypericin downregulated the formation of AGEs and ameliorated MGO-induced dysfunction in human endothelial cells.

• Korean Journal of Pharmacognosy
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• v.50 no.1
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• pp.25-31
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• 2019

The zebrafish (Danio rerio) is an established model organism for several pathophysiological conditions which are related to human diseases. In this study, we tested the preventive effect of eight herbal extracts, which show the inhibitory effect of advanced glycation end products (AGEs) or aldose reductase (AR) in our previous study, on high glucose (HG)-induced retinal vessel dilation in larval zebrafish and analyzed the change of hyaloid vasculature. HG-induced zebrafish hyaloid vasculatures were significantly increased in the thickness compared to untreated zebrafish (P<0.001, n=6~10). Eight herbal extracts were found to have significant retinal vessel dilation on the inhibitory activity. Particularly, Brandisia hancei (twigs and fruits), Castanopsis orthacantha (leaves and twigs), Litsea japonica (leaves and twigs), Spenceria ramalana (whole plant), and Synedrella nodiflora (leaves and stems) showed potent inhibitory activity against retinal vessel dilation in HG-induced larval zebrafish.

• Molecules and Cells
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• v.45 no.12
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• pp.869-876
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• 2022

Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential antitumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathionedependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

• Biodesign
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• v.5 no.3
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• pp.122-125
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• 2017

Receptor for advanced glycation end products (RAGE) is one of the single transmembrane domain containing receptors and causes various inflammatory diseases including diabetes and atherosclerosis. RAGE extracellular domain has three consecutive IgG-like domains (V-C₁-C₂ domain) which interact with various soluble ligands including heparan sulfate or HMGB1. Studies have shown that each ligand induces different oligomeric forms of RAGE which results in a ligand-specific signal transduction. The structure of mouse RAGE bound to heparan sulfate has been previously determined but the electron density map of heparan sulfate was too ambiguous that the exact position of heparin sulfate could not be defined. Furthermore, the complex structure of human RAGE and heparin sulfate still remains elusive. Therefore, to determine the structure, human RAGE was overexpressed using bacterial expression system and crystallized using the sitting drop method in the condition of 0.1 M sodium acetate trihydrate pH 4.6, 8 % (w/v) polyethylene glycol 4,000 at 290 K. The crystal diffracted to 3.6 Å resolution and the space group is C121 with unit cell parameters a= 206.04 Å, b= 68.64 Å, c= 98.73 Å, α= 90.00°, β= 90.62°, γ= 90.00°.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.1025-1036
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• 2008

Objectives : The aim of present study was to investigate recovery effects of gypsum, which has been used clinically in diabetes therapy. Methods : We established three groups, normal, control, and gypsum, and assigned 6 rats to each group. The normal group was not treated by any process and fed normal saline. The control & gypsum groups were administered streptozotocin(STZ) to induce diabetes. Gypsum extract was orally administered to the gypsum group for 10 days. After 8 weeks, the rats were sacrificed and their body weight, 24hrs urinary protein excretion, glucose, albumin, BUN, creatinine, total-cholesterol, LDL-cholesterol, triglyceride in blood, level of glycation end-product (AGE) and transforming growth factor ($TGF-{\beta}1$) in serum were measured. Morphological profiles and morphometric studies of the kidney cortex. renal transforming growth factor ($TGF-{\beta}1$) expression, macrophage/monocyte antigen (ED-1), and type IV collagen expression were studied. Results : The following results were obtained. The protein amount in urine per 24hrs of the gypsum-treated group as compared to the control was significantly reduced. The BUN and creatinine level in serum of the gypsum-treated group as compared to the control was significantly inhibited. The construction change in the kidneys of the gypsum-treated group as compared to the control was significantly inhibited. The factor of the gypsum-treated group as compared to the control was significantly inhibited. which induced the structural change in the kidneys. Conclusions : The above results suggest that gypsum partially improved kidney function.