• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.60-70
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• 2015

In this study, we investigated the effects of cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha on collagen-stimulated platelet aggregation. CE-WIB801C dose dependently inhibited collagen-induced platelet aggregation, and had a synergistic effect together with cordycepin (W-cordycepin) from CE-WIB801C on the inhibition of collagen-induced platelet aggregation. CE-WIB801C and cordycepin stimulated the phosphorylation of VASP ($Ser^{157}$) and the dephosphorylation of PI3K and Akt, and inhibited the binding of fibrinogen to glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}3$) and the release of ATP and serotonin in collagen-induced platelet aggregation. A-kinase inhibitor Rp-8-Br-cAMPS reduced CE-WIB801C-, and cordycepin-increased VASP ($Ser^{157}$) phosphorylation, and increased CE-WIB801C-, and cordycepin-inhibited the fibrinogen binding to ${\alpha}IIb/{\beta}3$. Therefore, we demonstrate that CE-WIB801C-, and cordycepin-inhibited fibrinogen binding to ${\alpha}IIb/{\beta}3$are due to stimulation of cAMP-dependent phosphorylation of VASP ($Ser^{157}$), and inhibition of PI3K/Akt phosphorylation. These results strongly indicate that CE-WIB801C and cordycepin may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• The Journal of Internal Korean Medicine
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• v.35 no.4
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• pp.505-518
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• 2014

Objectives: This study was undertaken to investigate the effects of Gugijagami-bang (GGB) in a hyperlipidemic animal model induced by a high-fat diet using diverse biological methods. Methods: This study was to determine whether fractionated GGB extracts inhibit reactive oxygen species (ROS) and nitric oxide (NO) in RAW 264.7 cells. Hyperlipidemia was induced by a high-fat diet fed for 6 weeks. Total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, liver function and histologic change of liver were measured after oral administration of GGB. Results: 1. DPPH scavenging bow performance was increased in a concentration-dependent manner by GGB. 2. Compared to the control group, NO production (%) and ROS production (%) were decreased significantly by GGB. 3. Total-cholesterol, LDL-cholesterol, triglyceride were decreased significantly by GGB. 4. HDL cholesterol increased more than the control group, but not significantly. 5. In histopathologic examination, fatty liver (hepatic steatosis) was inhibited, almost no rounds of fat were observed in the liver. Conclusions: GGB would appear effective in the prevention and treatment of atherosclerosis, ischemic heart disease, other cardiovascular diseases caused by hyperlipidemia.

• Journal of Haehwa Medicine
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• v.12 no.2
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• pp.1-9
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• 2004

1. Purpose Stroke is the most frequent cause of mortality and morbidity rate in Korea with coronary heart disease and cancer. The ischemic type of stroke is increasing tendency. The purpose of this studies is to examine the hematologic difference between cb infarction patients and Korean normal adults. 2. Method The study group consisted of neurologically confirmd 50 cb-infarction patients as the case group and 278 patients as control group that they had no significant result by CT through early examination of stroke in Cheonan oriental hospital of Daejeon university. We tested and compared RBC, hemoglobin, hematocrit, WBC, PT, PTT, total protein, albumin, total bilirubin, direct bilirubin, GOT GPT, $\gamma$-GTP, total cholesterol, triglyceride, HDL-C, glucose, BUN, creatinine, Na, K in the both group. 3. Result In the sample group(cb infarction group), there were many patients with low RBC count but no significant and with low hemoglobin, hematocrit(p<0.05). Thereas, increased WBC count and delayed PTT were showed respectively 20%, 36% in patient group, 7.9%, 4.7% in normal group(p<0.05). Comparing the LFT between cb infarction patients and normal adults, we founded significant cases with low HDL-C level, high glucose level, low potassium level in patient group(p<0.05). But the percentage of high total cholesterol level and triglyceride level were 18%, 29%(norma1 group), 20%, 28%(cb infarction group) respectively, there were no significant difference. 4. Conclusion In this study, we demonstrated that low HDL-C level and high glucose level is one of important risk factor of cb infarction. Also prospective studies are needed to evaluate many risk factor(hemoglobin, hematocrit, WBC, cholesterol, triglyceride, K, etc) of cb infarction.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.2
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• pp.91-97
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• 2010

Epidermal keratinocytes overgrow in response to ultraviolet-B (UVB), which may be associated with skin photoaging and cancer development. Recently, we found that HIF-$1{\alpha}$ controls the keratinocyte cell cycle and thereby contributes to epidermal homeostasis. A further study demonstrated that HIF-$1{\alpha}$ is down-regulated by UVB and that this process is involved in UVB-induce skin hyperplasia. Therefore, we hypothesized that the forced expression of HIF-$1{\alpha}$ in keratinocytes would prevent UVB-induced keratinocyte overgrowth. Among several agents known to induce HIF-$1{\alpha}$, pyrithione-zinc (Py-Zn) overcame the UVB suppression of HIF-$1{\alpha}$ in cultured keratinocytes. Mechanistically, Py-Zn blocked the degradation of HIF-$1{\alpha}$ protein in keratinocytes, while it did not affect the synthesis of HIF-$1{\alpha}$. Moreover, the p21 cell cycle inhibitor was down-regulated after UVB exposure, but was robustly induced by Py-Zn. In mice repeatedly irradiated with UVB, the epidermis became hyperplastic and HIF-$1{\alpha}$ disappeared from nuclei of epidermal keratinocytes. However, a cream containing Py-Zn effectively prevented the skin thickening and up-regulated HIF-$1{\alpha}$ to the normal level. These results suggest that Py-Zn is a potential agent to prevent UVB-induced photoaging and skin cancer development. This work also provides insight into a molecular target for treatment of UVB-induced skin diseases.

• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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• pp.1-8
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• 2005

Clopidogrel is used to reduce the risk of cardiovascular events in patients with atherosclerosis documented by recent ischemic stroke, recent myocardial infarction (MI), or established peripheral arterial disease (secondary prevention). Clopidogrel is metabolized by CYP3A4, and the active metabolites inhibit platelet aggregation. The purpose of this study was to assess clopidogrel only versus clopidogrel + others (aspirin, CYP3A4 inhibitor, and CYPBA4 inducer) in terms of cardiovasculalr events and bleeding complications. We reviewed the charts of patients who visited between August 1, 2002 and August 31, 2003, retrospectively. Total 72 patients were included and they consisted of 5 groups; clopidogrel group (n=36), clopidogrel + aspirin group (n=11), clopidogrel + CYP3A4 inhibitor group (n=15), clopidogrel + aspirin + CYP3A4 inhibitor group (n=6), clopidorel + CYP3A4 inducer group (n=4). The primary endpoints at 6 months, 12 months were the composite of cardiovascular (CV) events. The secondary end-point was the incidence of bleeding events at 6months, and 12months. At 12months, the primary endpoint was not significantly different among the five groups (p=0.056). In comparison of two groups as clopidogrel only versus clopidogrel + others (aspirin, CYP3A4 inhibitor and CYP3A4 inducer), the primary endpoint was significantly different (p=0.02). The CV events were increased in the clopidogrel + others group. The secondary end point was not significantly different among the five groups (p=0.52). However, time to bleeding events was 230.8 in the clopidogrel group and 74.7 in the clopidogrel + others group (p = 0.046). In conclusion, clopidogrel interaction with aspirin, CYP3A4 inhibitor, and CYP3A4 inducer affected cardiovascular events and bleeding events. Drug interaction of clopidogrel with concurrent medications should be considered cautiously.

• Biomedical Science Letters
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• v.21 no.2
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• pp.103-114
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• 2015

In this study, we investigated the effect of rice bran water extract fermented with Lactobacillus plantarum KCCM-12116 (RBLp) on ADP ($20{\mu}M$)-, collagen ($10{\mu}g/mL$)-, and thrombin (0.2 U/mL)-stimulated platelet aggregation. RBLp dose-dependently inhibited ADP-, collagen-, and thrombin-induced platelet aggregation, with $IC_{50}$ values of 501.1, 637.2, and > $2,000{\mu}g/mL$, respectively. The platelet aggregation induced by ADP plus RBLp ($750{\mu}g/mL$) was increased by the adenylate cyclase inhibitor, SQ22536, and the cAMP-dependent protein kinase (A-kinase) inhibitor, Rp-8-Br-cAMPS. Treatment with RBLp increased the phosphorylation of VASP ($Ser^{157}$), an A-kinase substrate, which was also inhibited by SQ22536 and Rp-8-Br-cAMPS. It is thought that the RBLp-induced increases in cAMP contributed to the phosphorylation of VASP ($Ser^{157}$), which in turn resulted in an inhibition of ADP-induced platelet aggregation, thereby indicating that RBLp has an antiplatelet effect via cAMP-dependent phosphorylation of VASP ($Ser^{157}$). Thus, RBLp may have therapeutic potential for the treatment (or prevention) of platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• The Journal of Internal Korean Medicine
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• v.21 no.3
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• pp.369-376
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• 2000

Purpose : Cerebrovascular disease is the most frequent cause of death in Korea and it remains severe disabilities disturbing normal life, According to the previous studies, mortality of the stroke in the first one week is up to the 20% and 95% of stroke patients in the acute stage are accompanied by more than one complications. These complications affect not only the acute stage mortality but also the late stage rehabilitations. In Korea the oriental medicine is preformed in the treatment of stroke. Therefore it is important to recognize thoroughly the complications in the acute stage of stroke and to prevent them. But studies about complications of acute stage stroke is rarely presented in the fields of oriental medicine. So this study is prepared for investigating the characteristics and frequency of complications in the acute stage of stroke. And we are to assess the importance of theses acute complications by systemic reviewing the previous studies. Methods : Fifty one patients are included who had been admitted to ICU(intensive care unit) of Chenju Hospital of Wonkwang Oriental Medicine. Twenty nine patients are diagnosed as ischemic stroke and twenty one patients are diagnosed hemorrhagic stroke. Medical and neurological complications were investigated retrospectively based on medical notes excluding primary symptoms of stroke Le. motor weakness, sensory disturbance and speech disorder. And risk factors of stroke such as D.M. or hypertension are excluded. Results : Medical complications are more frequent than neurological ones. Most frequent medical complication is dysuria(61%) and constipation(45%), fever(30%) and aspiration pneumonia(22%) are followed in order of frequency. In Neurological complication dysphagia(56%), the exacerbation of infarction due to increased intracranial pressure(24%), irritability or insomnia(21%) is most frequently complicated in order of frequency. Conclusions : These complications are mostly caused by bed rest state in acute stage stroke. It is supposed that more aggressive management can prevent theses ones. And it is possible to improve the medical and neurological conditions by sticking theses study results.

• The Journal of Internal Korean Medicine
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• v.39 no.4
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• pp.480-494
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• 2018

Objectives: To investigate the effect of fermented extract of Artemisiae Iwayomogii Herba, Curcumae Longae, Crataegi Fructus and Salviae Miltiorrhizae Radix (FMH) on anti-inflammation associated with dyslipidemia and anti-oxidation in RAW264.7 and HUVEC cells. Methods: The total polyphenols, total flavonoids, DPPH radical scavenging activity, ABTS radical scavenging activity, and cytotoxicity of FMH were measured. RAW264.7 cells treated with FMH were tested for production of NO, and for cytokine and LTB4 levels and HUVEC cells treated with FMH were examined for production of cDNA of genes related to inflammation. Results: 1. FMH contained polyphenols and flavonoids. The DPPH and ABTS radical scavenging activity of FMH increased in a concentration-dependent manner. 2. FMH treatment inhibited the production of nitric oxide (NO), cytokines, and LTB4 in RAW264.7 cell when compared to the untreated control group. 3. FMH decreased the transcription of pro-inflammatory genes, whereas it increased transcription of anti-inflammatory genes, in HUVEC cells. Conclusion: FMH is effective as an antioxidant and for treatment and prevention of dyslipidemia, atherosclerosis, ischemic heart disease, stroke, and other cardiocerebrovascular diseases.

• Journal of Korean Society for Quality Management
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• v.39 no.3
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• pp.391-399
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• 2011

Our study was carried out to analyze the variation factors of severity-adjusted length of stay(LOS) in coronary artery bypass graft(CABG). The subjects were 932 CABG inpatients of the Korean National Hospital Discharge In-depth Injury Survey from 2004 through 2008. The data were analyzed using $x^2$ test and the severity-adjusted model was developed using data mining technique. The results of the study were as follows: male(71.1%), older than 61 years of age(61.6%), more than 500 beds(92.8%) and admitting via ambulatory care(70.0%) appeared to have higher rate than otherwise. In-hospital mortality of CABG inpatients was 2.8%. In addition, 46.4% of the patients received their care in other residence. The angina pectoris(45.6%) was found to be the highest in principle diagnosis, followed by chronic ischemic heart disease(36.9%) and acute myocardial infarction(12.0%). We developed severity-adjusted LOS model using the variables such as gender, age and comorbidity. Comparison of adjusted values in predicted LOS revealed that there were significant variations in LOS by location of hospital, bed size, and whether patients received the care in their residences. The variations of LOS can be explained as the indirect indicator for quality variation of medical process. It is suggested that the severity-adjusted LOS model developed in this study should be utilized as a useful method for benchmarking in hospital and it is necessary that national standard clinical practice guideline should be developed.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.260-267
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• 2016

Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes increased in a time-dependent manner. After re-attachment of MSC spheroids to the plastic dish, their adhesion capacity and morphology were not altered. MSC spheroids showed enhanced production of hypoxia-induced angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF), and hepatocyte growth factor (HGF). In addition, spheroid culture promoted the preservation of extracellular matrix (ECM) components, such as laminin and fibronectin, in a culture time- and spheroid size-dependent manner. Furthermore, phosphorylation of AKT, a cell survival signal, was significantly higher and the expression of pro-apoptotic molecules, poly (ADP ribose) polymerase-1 (PARP-1) and cleaved caspase-3, was markedly lower in the spheroids than in MSCs in monolayers. In the murine hindlimb ischemia model, transplanted MSC spheroids showed better proliferation than MSCs in monolayer. These findings suggest that MSC spheroids promote MSC bioactivities via secretion of angiogenic cytokines, preservation of ECM components, and regulation of apoptotic signals. Therefore, MSC spheroid-based cell therapy may serve as a simple and effective strategy for regenerative medicine.