• Nutritional Sciences
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• v.9 no.1
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• pp.3-8
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• 2006

Functional damage to microvascular endothelial cells by hyperglycemia is thought to be one of the critical risk factor.; in the impaired wound healing seen with diabetes mellitus. It is also thought that oxidative stress plays a significant role in this endothelial cell dysfunction. The present study examined the differential effects of flavonoids on endothelial cell dysfunction under high glucose conditions. Human endothelial cells exposed to 30 mmol/L glucose for 7 d were pre-treated with various flavonoids and pulse-treated with 0.2 mmol/L $H_2O_2$ for 30 min. High glucose markedly decreased cell viability with elevated oxidant generation and nuclear condensation. $H_2O_2$ insult exacerbated endothelial cytotoxicity due to chronic exposure to high glucose. (-)Epigallocatechin gallate and quercetin improved glucose-induced cell damage with the disappearnnce of apoptotic bodies, whereas apigenin intensified the glucose cytotoxicity. In addition, cell viability data revealed that these flavonoids of (-)epigallocatechin gallate and quercetin substantially attenuated both high glucose- and $H_2O_2$- induced dual endothelial damage. These results suggest that (-)epigallocatechin gallate and quercetin may be beneficial agents for improving endothelial cell dysfunction induced by high glucose and may prevent or reduce the development of diabetic vascular complications.

• BMB Reports
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• v.39 no.5
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• pp.469-478
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• 2006

Vascular endothelial growth factor (VEGF)-A, a major regulator for angiogenesis, binds and activates two tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). These receptors regulate physiological as well as pathological angiogenesis. VEGFR2 has strong tyrosine kinase activity, and transduces the major signals for angiogenesis. However, unlike other representative tyrosine kinase receptors which use the Ras pathway, VEGFR2 mostly uses the Phospholipase-$C{\gamma}$-Protein kinase-C pathway to activate MAP-kinase and DNA synthesis. VEGFR2 is a direct signal transducer for pathological angiogenesis including cancer and diabetic retinopathy, thus, VEGFR2 itself and the signaling appear to be critical targets for the suppression of these diseases. VEGFR1 plays dual role, a negative role in angiogenesis in the embryo most likely by trapping VEGF-A, and a positive role in adulthood in a tyrosine kinase-dependent manner. VEGFR1 is expressed not only in endothelial cells but also in macrophage-lineage cells, and promotes tumor growth, metastasis, and inflammation. Furthermore, a soluble form of VEGFR1 was found to be present at abnormally high levels in the serum of preeclampsia patients, and induces proteinurea and renal dysfunction. Therefore, VEGFR1 is also an important target in the treatment of human diseases. Recently, the VEGFR2-specific ligand VEGF-E (Orf-VEGF) was extensively characterized. Interestingly, the activation of VEGFR2 via VEGF-E in vivo results in a strong angiogenic response in mice with minor side effects such as inflammation compared with VEGF-A, suggesting VEGF-E to be a novel material for pro-angiogenic therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.347-355
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• 2022

Abdominal aortic aneurysm (AAA) is a life-threatening disorder worldwide. Fibroblast growth factor 21 (FGF21) was shown to display a high level in the plasma of patients with AAA; however, its detailed functions underlying AAA pathogenesis are unclear. An in vitro AAA model was established in human aortic vascular smooth muscle cells (HASMCs) by angiotensin II (Ang-II) stimulation. Cell counting kit-8, wound healing, and Transwell assays were utilized for measuring cell proliferation and migration. RT-qPCR was used for detecting mRNA expression of FGF21 and activating transcription factor 4 (ATF4). Western blotting was utilized for assessing protein levels of FGF21, ATF4, and markers for the contractile phenotype of HASMCs. ChIP and luciferase reporter assays were implemented for identifying the binding relation between AFT4 and FGF21 promoters. FGF21 and ATF4 were both upregulated in Ang-II-treated HASMCs. Knocking down FGF21 attenuated Ang-II-induced proliferation, migration, and phenotype switch of HASMCs. ATF4 activated FGF21 transcription by binding to its promoter. FGF21 overexpression reversed AFT4 silencing-mediated inhibition of cell proliferation, migration, and phenotype switch. ATF4 transcriptionally upregulates FGF21 to promote the proliferation, migration, and phenotype switch of Ang-II-treated HASMCs.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.629-639
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• 2023

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.

• Annals of Clinical Neurophysiology
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• v.12 no.2
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• pp.66-69
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• 2010

A 73-year-old man with progressive quadriparesis was diagnosed as Guillain-Barr$\acute{e}$ syndrome. On the 6th hospital day, the patient complained of sudden chest discomfort. The blood test and echocardiography suggested myocardial injury, and acute myocardial infarction was considered. However, coronary angiography displayed no vascular lesion, and the electrocardiography and echocardiogram showed marked improvement 14 days later. We concluded the patient had a reversible cardiomyopathy which is a rare complication of Guillain-Barr$\acute{e}$ syndrome.

• Childhood Kidney Diseases
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• v.21 no.1
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• pp.26-30
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• 2017

Newborn infants with huge and highly vascular sacrococcygeal teratoma (SCT) are frequently subjected to renal hypoperfusion secondary to high-output cardiac failure. Any underlying renal dysfunction is a significant risk factor for the development of contrast-induced nephropathy (CIN). However, reports on CIN in infants are rare. I report here a case of a premature infant born at 28 weeks and 3 days of gestation with a huge SCT who survived preoperative embolization and surgical resection but presented with persistent non-oliguric renal failure that was suggestive of CIN. During radiological intervention, a contrast medium had been administered at about 10 times the manufacturer-recommended dose for pediatric patients. Despite hemodynamic stabilization and normalization of urine output immediately following surgery, the patient's serum creatinine and cystatin-C levels did not return to baseline until 4 months after birth. No signs of reflux nephropathy were observed in follow-up imaging studies. Dosing guidelines for the use of a contrast medium in radiological interventions should be provided for infants or young patients.

• Journal of Oriental Neuropsychiatry
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• v.10 no.2
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• pp.105-113
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• 1999

The purpose of this study was to investigate the effect of Sunhyangjungkisan on the learning and memory ability in rats. For this purpose we have evoked cerebral dysfunction in rats with NOS inhibitor and then performed the Morris water maze task for each rat. We have found that Sunghyangjungkisan have some improving effedts on impaired learning and memort ability in the NOS inhibitor treated rat. In these improving effects, memory effect was more evident then learning effect. This result implies that Sunghyangjungkisan may be one of useful prescriptions for treatment of vascular dementia after cerebral ischemia.

• Journal of Korean Neurosurgical Society
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• v.47 no.3
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• pp.210-212
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• 2010

Sildenafil citrate ($Viagra^{(R)}$ Pfeizer US Pharmaceutical Group, New York, NY, USA) is a potent vasodilating agent to treat male erectile dysfunction. Among its adverse effects, hemorrhagic stroke has not been widely reported yet. We present a case of a 33-year-old healthy man who ingested 50 mg sildenafil a half hour before onset of headache, nervousness and speech disturbance. Head computed tomogram of this stuporous man showed huge intracerebral hemorrhage and thick subarachnoid hemorrhage, but angiography failed to disclose any vascular anomalies. Subsequent surgical procedure was followed, and rehabilitation was provided thereafter. Sildenafil seems to act by redistributing arterial blood flow, and concurrent sympathetic hyperactivity, which lead to such hemorrhagic presentation. Extreme caution should be paid on even in a young adult male patient wven without known risk factors.

• Preventive Nutrition and Food Science
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• v.18 no.1
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• pp.11-17
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• 2013

Dysfunction of endothelial cells is considered a major cause of vascular complications in diabetes. In the present study, we investigated the protective effect of Padina arborescens extract against high glucose-induced oxidative damage in human umbilical vein endothelial cells (HUVECs). High-concentration of glucose (30 mM) treatment induced cytotoxicity whereas Padina arborescens extract protected the cells from high glucose-induced damage and significantly restored cell viability. In addition, lipid peroxidation, intracellular reactive oxygen species (ROS), and nitric oxide (NO) levels induced by high glucose treatment were effectively inhibited by treatment of Padina arborescens extract in a dose-dependent manner. High glucose treatment also induced the overexpressions of inducible nitric oxide synthase (iNOS), cyclooxygenase- 2 (COX-2) and NF-${\kappa}B$ proteins in HUVECs, but Padina arborescens extract treatment reduced the over-expressions of these proteins. These findings indicate the potential benefits of Padina arborescens extract as a valuable source in reducing the oxidative damage induced by high glucose.

• Journal of Chest Surgery
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• v.44 no.1
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• pp.72-75
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• 2011

Aortic thrombi are important because it can cause the central and peripheral embolizations. Aortic thrombi can occur anywhere in the aorta but extremely rare in ascending aorta without atherosclerosis, aneurysm, cardiosurgical or traumatic state. Systemic sclerosis (SSc) is an autoimmune disorder of connective tissue and it can involve multisystem. Enhanced coagulation pathways, decreased fibrinolysis, and endothelial dysfunction probably contribute to vascular events in SSc. We report a case of a highly mobile thrombus in the ascending aorta, presented as an acute embolic stroke in the patient with systemic sclerosis. Surgical removal was performed to prevent recurrent embolic events.