• Title/Summary/Keyword: Advanced age

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Sildenafil Ameliorates Advanced Glycation End Products-Induced Mitochondrial Dysfunction in HT-22 Hippocampal Neuronal Cells

  • Sung, Soon Ki;Woo, Jae Suk;Kim, Young Ha;Son, Dong Wuk;Lee, Sang Weon;Song, Geun Sung
    • Journal of Korean Neurosurgical Society
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    • v.59 no.3
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    • pp.259-268
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    • 2016
  • Objective : Accumulation of advanced glycation end-products (AGE) and mitochondrial glycation is importantly implicated in the pathological changes of the brain associated with diabetic complications, Alzheimer disease, and aging. The present study was undertaken to determine whether sildenafil, a type 5 phosphodiesterase type (PDE-5) inhibitor, has beneficial effect on neuronal cells challenged with AGE-induced oxidative stress to preserve their mitochondrial functional integrity. Methods : HT-22 hippocampal neuronal cells were exposed to AGE and changes in the mitochondrial functional parameters were determined. Pretreatment of cells with sildenafil effectively ameliorated these AGE-induced deterioration of mitochondrial functional integrity. Results : AGE-treated cells lost their mitochondrial functional integrity which was estimated by their MTT reduction ability and intracellular ATP concentration. These cells exhibited stimulated generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, induction of mitochondrial permeability transition, and release of the cytochrome C, activation of the caspase-3 accompanied by apoptosis. Western blot analyses and qRT-PCR demonstrated that sildenafil increased the expression level of the heme oxygenase-1 (HO-1). CoPP and bilirubin, an inducer of HO-1 and a metabolic product of HO-1, respectively, provided a similar protective effects. On the contrary, the HO-1 inhibitor ZnPP IX blocked the effect of sildenafil. Transfection with HO-1 siRNA significantly reduced the protective effect of sildenafil on the loss of MTT reduction ability and MPT induction in AGE-treated cells. Conclusion : Taken together, our results suggested that sildenafil provides beneficial effect to protect the HT-22 hippocampal neuronal cells against AGE-induced deterioration of mitochondrial integrity, and upregulation of HO-1 is involved in the underlying mechanism.

Signaling Interface of Advanced Glycation Endproducts Receptor and Ubiquitin-Conjugating Enzyme Ubc9 Complex in Atherosclerosis and Cancer Cells

  • Kim, June Hyun
    • Interdisciplinary Bio Central
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    • v.4 no.4
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    • pp.13.1-13.6
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    • 2012
  • The advanced glycation endproducts receptor (AGER) is a multiligand signal transduction receptor. One of its ligands, S100b molecules activates vascular smooth muscle cells and endothelial cells via its receptor, thus triggering activation of signaling cascades and generation of cytokines and proinflammatory molecules. Ubiquitin-conjugating enzyme Ubc9 is an E2 conjugating enzyme that transfers the activated small ubiquitin-related modifier to protein substrates, and thus it plays a critical role in SUR-Mylation-mediated cellular pathways. Previous studies have shown that both AGE-R and Ubc9 play roles in diverse cellular signaling pathways. However, until recently, little attention has been paid to interactions between AGE-R and Ubc9. In this study, sequence database searches allowed us to identify a potential interaction motif between AGE-R and Ubc9. The subsequent biochemical and molecular biological analysis suggested that there may be specificity in AGE-R and Ubc9 complex signaling in atherosclerosis and cancer cells in a cell-type specific manner. Although the determinant for specificity in AGE-R and Ubc9 complex signaling in cancer cells and atherosclerosis is yet to be determined, this study provides the basis to develop a specific therapeutic application of AGE-R, SURM (small ubiquitin-related modifier)-1, and Ubc9 complex activation pathways in atherosclerosis, diabetes, cancer and inflammatory diseases.

Safe and Comfortable Electromotive Cart for People of Advanced Age

  • Kuc, Tae-Yong;Tefsuya, Muraoka
    • 제어로봇시스템학회:학술대회논문집
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    • 2001.10a
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    • pp.85.5-85
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    • 2001
  • When the people of advanced age drive the public electromotive cart of tricycle type on the slant and bumpy roads, the viewing angle of driver changes at the different directions. So the risk of traffic accident is increased. For the improvement of the above problem, we had produced the first experimental cart installed to the new driver´s seat based on the 2$\pi$ control theory. Based on the results of the driving test for the first experimental cart, we have produced the safe and comfortable electromotive cart.

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The ]Relationship between Strain Ageing And Delamination Occurrence of Drawn Steel Wires (신선가공 고탄소 강선에서의 시효현상과 딜라미네이션 발생간의 상관관계 고찰)

  • Lee, J.W.;Lee, J.C.;Gang, U.G.;Lee, Y.S.;Park, K.T.;Nam, W.J.
    • Proceedings of the Korean Society for Technology of Plasticity Conference
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    • 2009.05a
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    • pp.231-234
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    • 2009
  • The effects of annealing temperature and time on mechanical properties and microstructures were already investigated in cold drawn pearlitic steel wires. During annealing, the increment of the tensile strength at low temperatures found to be due to age hardening, while the decrease in the tensile strength at high temperatures was attributed to age softening, involving the spheroidization of lamellar cementite and recovery of lamellar ferrite. Since Between increase of tensile strength and the occurrence of the delamination would be closely related to the dissolution of cementite, the increase of drawing strain by lower annealing temperature caused the between higher tensile strength and the easier occurrence of the delamination in cold drawn pearlitic steel wires.

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The Bioinformatics and Molecular Biology Approaches for Vascular Cell Signaling by Advanced Glycation Endproducts Receptor and Small Ubiquitin-Related Modifier

  • Kim, June Hyun
    • Interdisciplinary Bio Central
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    • v.4 no.4
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    • pp.12.1-12.6
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    • 2012
  • The advanced glycation endproducts receptor (AGE-R) is a signal transduction receptor for multiligand such as S100b and AGEs. S100b has been demonstrated to activate various cells with important links to atherosclerosis initiation and progression including endothelial cells, and smooth muscle cells via AGE-R, triggering activation of multiple signaling cascades through its cytoplasmic domain. Many studies have suggested AGE-R might even participate in the cardiovascular complications involved in the pathogenesis of type I diabetes. Recently, Small Ubiquitin-Related Modifier 1 (SURM-1 also known as SUMO-1) has been recognized as a protein that plays an important role in cellular post-translational modifications in a variety of cellular processes, such as transport, transcriptional, apoptosis and stability. Computer Database search with SUMOplot Analysis program identified the five potential SURMylation sites in human AGE-R: K43, K44, K123, and K273 reside within the extracellular domain of AGE-R, and lastly K374 resides with the cytosolic domain of AGE-R. The presence of the consensus yKXE motif in the AGE-R strongly suggests that AGE-R may be regulated by SURMylation process. To test this, we decided to determine if AGE-R is SURMylated in living vascular cell system. S100b-stimulated murine aortic vascular smooth muscle cells were used for western blot analysis with relevant antibodies. Taken together, bioinformatics database search and molecular biological approaches suggested AGE-R is SURMylated in living cardiovascular cell system. Whilst SURMylation and AGE-R undoubtedly plays an important role in the cardiovascular biology, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.

Role of Advanced Glycation End Products in TGF-β1 and Fibronectin Expression in Mesangial Cells Cultured under High Glucose

  • HA Hunjoo;KIM Hwa-Jung;LEE Hi Bahl
    • Biomolecules & Therapeutics
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    • v.13 no.3
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    • pp.190-197
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    • 2005
  • Advanced glycation end products (AGE) have been implicated in the pathogenesis of diabetic complications including nephropathy. However, the role of AGE in the activation of mesangial cells cultured under high glucose has not been elucidated. The effects of aminoguanidine, which prevents formation of AGE and protein cross-linking, on the synthesis of $TGF-{\beta}1$ and fibronectin by rat mesangial cells cultured under high glucose for 2 weeks were examined and compared with the effects of $N^G$-nitro-L-arginine methyl ester (NAME), a selective nitric oxide synthase inhibitor, because aminoguanidine also inhibits the inducible nitric oxide synthase. Culture of mesangial cells in 30 mM (high) glucose for 2 weeks induced 1.5-fold (ELISA) and 1.9-fold (Western blot analysis) increase in AGE in the culture media compared to 5.6 mM (control) glucose. Northern blot analysis revealed 1.5-fold increase in $TGF-{\beta}1$ and 1.7-fold increase in fibronectin mRNA expression in cells cultured under high glucose compared to control glucose. Increases in mRNA expression were followed by increased protein synthesis. Mink lung epithelial cell growth inhibition assay revealed 1.4-fold increase in $TGF-{\beta}1$ protein in high glucose media compared to control. Fibronectin protein also increased 2.1-fold that of control glucose by Western blot analysis. Administration of aminoguanidine suppressed AGE formation in a dose dependent manner and at the same time suppressed $TGF-{\beta}1$ and fibronectin synthesis by mesangial cells cultured in both control and high glucose. In contrast, NAME did not affect high glucose-induced changes. These findings support a role for AGE in high glucose-induced upregulation of $TGF-{\beta}1$ and fibronectin synthesis by mesangial cells.

Distribution of medical status and medications in elderly patients treated with dental implant surgery covered by national healthcare insurance in Korea

  • Lee, Kyungjin;Dam, Chugeum;Huh, Jisun;Park, Kyeong-Mee;Kim, Seo-Yul;Park, Wonse
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.17 no.2
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    • pp.113-119
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    • 2017
  • Background: The purpose of this study was to investigate the distribution of systemic diseases and medications in patients older than 65 years of age who visited the hospital for implant treatment, as well as to investigate basic information about surgical complications that may occur after insured implant treatment. Method: A total of 126 patients over 65 years of age were treated for implant surgery from October 1, 2013 to October 30, 2016. Electronic chart review was conducted to obtain medical records, which included sex, age, systemic diseases, medication(s) being taken, and control of the medications. Five patients were excluded due to lack of medical records giving information about systemic disease. Results: Of the 126 patients, 112 (88.9%) were taking medication due to systemic disease and 9 patients (7.1%) were not. The sex distribution was 71 women and 55 men and the highest proportion of patients were between 65 and 69 years old. The most common diseases were, from most to least frequent, hypertension, cardiovascular disease, diabetes, and osteoporosis. The drug groups that can cause major complications after dental treatment were classified as hemorrhagic, osteoporotic, and immunosuppressive agents, and were taken by 45 (35.7%), 22 (17.5%) and 4 (3.2%) patients, respectively. Conclusion: Given that 88.9% of the elderly patients who were eligible for insurance implant treatment had systemic disease, it is necessary to carefully evaluate patients' medical histories and their general conditions in order to prevent emergencies during implant surgery.

Phenolic Compounds from the Leaves of Homonoia riparia and their Inhibitory Effects on Advanced Glycation End Product Formation

  • Lee, Ik-Soo;Jung, Seung-Hyun;Kim, Chan-Sik;Kim, Jin Sook
    • Natural Product Sciences
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    • v.23 no.4
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    • pp.274-280
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    • 2017
  • In a search for novel treatments for diabetic complications from natural resources, we found that the ethyl acetate-soluble fraction from the 80% ethanol extract of the leaves of Homonoia riparia has a considerable inhibitory effect on advanced glycation end product (AGE) formation. Bioassay-guided isolation of this fraction resulted in identification of 15 phenolic compounds (1 - 15). These compounds were evaluated in vitro for inhibitory activity against the formation of AGE. The majority of tested compounds, excluding ethyl gallate (15), markedly inhibited AGE formation, with $IC_{50}$ values of $2.2-89.9{\mu}M$, compared with that of the positive control, aminoguanidine ($IC_{50}=962.3{\mu}M$). In addition, the effects of active isolates on the dilation of hyaloid-retinal vessels induced by high glucose (HG) in larval zebrafish was investigated; (-)-epigallocatechin-3-O-gallate (6), corilagin (7), and desmanthine-2 (11) significantly decreased HG-induced dilation of hyaloid-retinal vessels compared with the HG-treated control group.

Anti-inflmmatory Effects of Scutellaria baicalensis Georgi Water Extract in the THP-1 Cells Activated by Advanced Glycation End Products (황금 물추출물의 당화종말산물로 유도한 THP-1 세포의 염증반응 억제효과)

  • Park, Pyeong-Beom;Kim, Min-Jun;Shin, Kyoung-Ho;Lee, Kwang-Gyu;Lee, Chang-Hyun;Lee, Sang-Ryong;Ha, Ki-Tae;Jeong, Han-Sol
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.3
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    • pp.273-280
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    • 2012
  • Scutellaria baicalensis Georgi, which has been known to be able to clear away heat and remove dampness, was used for febrile disease. It is now clear that Advanced glycation end products (AGEs) play major roles in the pathogenesis of diabetic complications such as atherosclerosis. In this study, we examined whether Scutellaria baicalensis Georgi suppress the AGE mediated inflammatory responses in the THP-1 cells. AGE treatment increased the gene expression of pro-inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), monocyte chemotactic protein-1 (MCP-1) and cyclooxygenase-2 (COX-2). Reverse transcriptase-polymerase chain reaction and Western blot analysis revealed that S. baicalensis had inhibitory effects on the expression of pro-inflammatory genes and protein levels in AGE-treated THP-1 cells. S. baicalensis had also reduced the production of ROS in the AGE-treated THP-1 cells. These results suggest that S. baicalensis has inhibitory effects for the development of diabetic vascular complication.

Foreign body aspiration and ingestion in dental clinic: a seven-year retrospective study

  • Huh, Jisun;Lee, Namkwon;Kim, Ki-Yeol;Jung, Seoyeon;Cha, Jungyul;Kim, Kee-Deog;Park, Wonse
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.22 no.3
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    • pp.187-195
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    • 2022
  • Background: This retrospective study investigated the incidence rate of accidental foreign body aspiration and ingestion according to patient sex, age, and dental department. This study aimed to verify whether the incidence rate is higher in geriatric than in younger patients and whether it is different among dental departments. Methods: Accidental foreign body aspiration and ingestion cases were collected from electronic health records and the safety report system of Yonsei University Dental Hospital from January 2011 to December 2017. The collected data included patients' age, sex, medical conditions, treatment procedures, and foreign objects that were accidentally aspirated or ingested. The incidence rate was calculated as the number of accidental foreign body aspirations and ingestions relative to the total number of patient visits. Differences depending on the patients' sex, age, and dental department were statistically identified. Results: There were 2 aspiration and 37 ingestion cases during the 7-year analysis period. The male to female incidence ratio was 2.8:1. The incidence rate increased with age and increased rapidly among those aged 80 years or older. Seven of the 37 patients with accidental foreign body ingestion had intellectual disability, Lou Gehrig's disease, dystonia, or oral and maxillofacial cancer. The incidence rate was highest in the Predoctoral Student Clinic and the Department of Prosthodontics. The most frequently swallowed objects were fixed dental prostheses and dental implant components. Conclusion: The incidence rate of accidental foreign body aspiration and ingestion differed according to patient sex, age, and dental department. Dental practitioners must identify high-risk patients and apply various methods to prevent accidental foreign body aspiration and ingestion in dental clinics. Inexperienced practitioners should be particularly careful.