• 한국체육학회지인문사회과학편
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• v.51 no.3
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• pp.363-372
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• 2012

One of the major ocular complications of diabetes mellitus(DM) is retinopathy, which is characterized by increased neovascularization and neural degeneration in the retina. In the present study, we investigated the effects of treadmill exercise on retinopathy in the rats with DM. Thirty-two male Sprague-Dawley rats were divided into four groups(n = 8 in each group): control group, exercise group, DM-induction group, and DM-induction and exercise group. DM was induced by intraperitoneal injection of streptozotocin. The rats in the exercise groups were made to run on the treadmill for 30 min five times per a week, during 12 weeks. The expressions of phosphoinositide 3-kinase(PI3K), phospho-protein kinase B(pAkt), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor(VEGF) in the retina were determined using western blot analysis and immunohistochemistry. In the present results, the expressions of PI3K, pAkt, HIF-1α, and VEGF in the retina of the diabetic rats were increased. Treadmill exercise suppressed HIF-1α and VEGF expressions through inhibition of PI3K/pAkt pathway in the diabetic rats. These results suggest that treadmill exercise may ameliorate the progression of diabetes-induced retinopathy by inhibiting neovascularization in the retina.

• Korean Journal of Radiology
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• v.24 no.4
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• pp.338-348
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• 2023

Objective: Patients with a history of ischemic stroke are at risk for a second ischemic stroke. This study aimed to investigate the relationship between carotid plaque enhancement on perfluorobutane microbubble contrast-enhanced ultrasonography (CEUS) and future recurrent stroke, and to determine whether plaque enhancement can contribute to risk assessment for recurrent stroke compared with the Essen Stroke Risk Score (ESRS). Materials and Methods: This prospective study screened 151 patients with recent ischemic stroke and carotid atherosclerotic plaques at our hospital between August 2020 and December 2020. A total of 149 eligible patients underwent carotid CEUS, and 130 patients who were followed up for 15-27 months or until stroke recurrence were analyzed. Plaque enhancement on CEUS was investigated as a possible risk factor for stroke recurrence and as a possible adjunct to ESRS. Results: During follow-up, 25 patients (19.2%) experienced recurrent stroke. Patients with plaque enhancement on CEUS had an increased risk of stroke recurrence events (22/73, 30.1%) compared to those without plaque enhancement (3/57, 5.3%), with an adjusted hazard ratio (HR) of 38.264 (95% confidence interval [CI]:14.975-97.767; P < 0.001) according to a multivariable Cox proportional hazards model analysis, indicating that the presence of carotid plaque enhancement was a significant independent predictor of recurrent stroke. When plaque enhancement was added to the ESRS, the HR for stroke recurrence in the high-risk group compared to that in the low-risk group (2.188; 95% CI, 0.025-3.388) was greater than that of the ESRS alone (1.706; 95% CI, 0.810-9.014). A net of 32.0% of the recurrence group was reclassified upward appropriately by the addition of plaque enhancement to the ESRS. Conclusion: Carotid plaque enhancement was a significant and independent predictor of stroke recurrence in patients with ischemic stroke. Furthermore, the addition of plaque enhancement improved the risk stratification capability of the ESRS.

• Journal of Microbiology and Biotechnology
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• v.11 no.4
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• pp.656-662
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• 2001

Angiogenesis is known as a crucial process in the growth and spreading of tumor cells. Accordingly, the effective inhibition of this process would appear to be a promising way to cure angiogenesis-related diseases, including cancer. This study demonstrates that acalycixenolide E (AX-E) from the marine organism Acalycigorgia inermis exhibits a potent anti-angiogenic activity both in vitro and in vivo. AX-E inhibits the bFGF-induced proliferation of HUVECs in a dose dependent manner, along with the bFGF-induced migration, invasion, and tube formation of HUVECs. Moreover, AX-E potently inhibits the in vivo neovascularization of the chorioallantoic membranes (CAMs) of growing chick embryos. interestingly, AX-E suppresses the expression of metalloproteases 2 and 9, yet shows no effect on their activities. The novel chemical structure and potent anti-angiogenic activity of AX-E will be of great value in elucidating the molecular mechanism of angiogenesis as well as in the development of a novel anti-angiogenic drug.

• The Journal of Korean Medicine
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• v.20 no.2
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• pp.128-140
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• 1999

To evaluate the antitumor activity, antimetastatic and immunomodulatory effects of samryongbakchulsankamibang(SBSK) studies were done experimentally, In cytotoxicity against P388, A549. SK-OV-3, B16-F10 and SK-MEL-2. concentration inhibiting cell growth up to below 40% of control was recognized at $10^{-3}g/ml$ of SBSK. In Inhibitory effect on activity of DNA topoisomerase I. the $IC_{50}$ was shown $200-400{\mu}g/ml$ of SBSK. The T/C was 154% in SBSK-treated group in S-180 bearing ICR mice, The concentration inhibiting adhesion of A549 and B16-F10 to complex extracellular matrix up to below 30% of control was recognized at $5{\times}10^{-4}$, $1{\times}10^{-3}\;g/ml$ of SBSK. In pumonary colonization assay with B16-BL/6, a number of colonies in the lungs were decreased significantly in SBSK-treated group as compared with control group, In hematological changes in B16-BL/6 injected C57BL/6, numbers of WBC and platelet were not changed significantly in SBSK-treated groups, In CAM and in vitro neovascularization assay, angiogenesis was inhibited significantly in SBSK-treated group as compared with control group. From above results it was concluded that SBSK could be usefully applied for the prevention and treatment of cancer.

• BMB Reports
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• v.51 no.7
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• pp.315-316
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• 2018

Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) system can be used as a tool to correct pathological mutations or modulate gene expression levels associated with pathogenesis of human diseases. Owing to well-established local administration methods including intravitreal and subretinal injection, it is relatively easy to administer therapeutic genome engineering machinery to ocular tissues for treating retinal diseases. In this context, we have investigated the potential of in vivo genome engineering as a therapeutic approach in the form of ribonucleoprotein or CRISPR packaged in viral vectors. Major issues in therapeutic application of genome engineering include specificity and efficacy according to types of CRISPR system. In addition to previous platforms based on ribonucleoprotein and CRISPR-associated protein 9 derived from Campylobacter jejuni, we evaluated the therapeutic effects of a CRISPR RNA-guided endonuclease derived from Lachnospiraceae bacterium ND2006 (LbCpf1) in regulating pathological angiogenesis in an animal model of wet-type age-related macular degeneration. LbCpf1 targeting Vegfa or Hif1a effectively disrupted the expression of genes in ocular tissues, resulting in suppression of choroidal neovascularization. It was also notable that there were no significant off-target effects in vivo.

• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.240-249
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• 2020

Despite the therapeutic effect of mesenchymal stem cells (MSCs) in ischemic diseases, pathophysiological conditions, including hypoxia, limited nutrient availability, and oxidative stress restrict their potential. To address this issue, we investigated the effect of melatonin on the bioactivities of MSCs. Treatment of MSCs with melatonin increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). Melatonin treatment enhanced mitochondrial oxidative phosphorylation in MSCs in a PGC-1α-dependent manner. Melatonin-mediated PGC-1α expression enhanced the proliferative potential of MSCs through regulation of cell cycle-associated protein activity. In addition, melatonin promoted the angiogenic ability of MSCs, including migration and invasion abilities and secretion of angiogenic cytokines by increasing PGC-1α expression. In a murine hindlimb ischemia model, the survival of transplanted melatonin-treated MSCs was significantly increased in the ischemic tissues, resulting in improvement of functional recovery, such as blood perfusion, limb salvage, neovascularization, and protection against necrosis and fibrosis. These findings indicate that the therapeutic effect of melatonin-treated MSCs in ischemic diseases is mediated via regulation of PGC-1α level. This study suggests that melatonin-induced PGC-1α might serve as a novel target for MSC-based therapy of ischemic diseases, and melatonin-treated MSCs could be used as an effective cell-based therapeutic option for patients with ischemic diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.667-673
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• 2002

The purpose of this study was to investigate the effect of Kamisamchulsamja-tang (KSST) water extract on the antitumor activity. The results were summarized as follows: KSST extract exhibited a weak cytotoxicity against HT1080, A549, SK-OV-3, B16-F10 and SK-MEL-2 cells. KSST extract showed a inhibitoty effect on DNA topoisomerase I from calf thymus in a dose-dependent manner. Also, KSST extract showed antiadhesive effect on HT1080 cells but didn't showed on A549 cells to complex extracellular matrix. In pumonary colonization assay, a number of colonies in the lungs were decreased significantly in KSST treated group as compared with control group. In vitro neovascularization assays, angiogenesis was significantly inhibited in KSST treated group than control group. In CAM assay, KSST extract inhibited angiogenesis significantly at 15㎍/egg concentration as compared with control. From the above results it was concluded that KSST showed antitumor effect through the antimetastatic effect. So it is expected to be clinically helpful on the prevention of metastasis of cancer.

• Journal of Veterinary Clinics
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• v.25 no.4
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• pp.263-267
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• 2008

This study was performed to compare the efficacy of carboxymethylchitosan fabric (CMCF) with that of the combination of CMCF and low molecular weight heparin (LMWH) for the prevention of postoperative uterine adhesion in rats. Adhesions were induced by suturing both the uterine serosa and peritoneum abrased until petechial bleeding occurred. Fourteen days later, adhesions were evaluated clinically and histopathologically. The mean tensile strength was significantly decreased in the CMCF and CMCF+LMWH groups compared to that of control group, and the CMCF+LMWH group had the lowest tensile strength. The distance of adhesion site was highest in the CMCF group and slightly decreased in the CMCF+LMWH group comparing to that of control group. The inflammatory cell infiltration and neovascularization of the CMCF group were significantly lower than those of the control group. It was observed that the damage at intestinal serosa was significantly decreased in the CMCF+LMWH group comparing to that of control group. Therefore, it was concluded that CMCF and LMWH may be useful to prevent postoperative uterine adhesion in rats.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.697-702
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• 2003

The purpose of this study was to investigate the effects of a protein-free, standardized dialysate/ultrafiltrate (HD) derivatives from calf blood (Solcoseryl$^{(R)}$) for second-intention full-thickness skin wound healing in dogs. Three $2{\times}2cm$ area-matched full-thickness skin wounds were created bilaterally on the dorsolateral aspect of the trunk of nine dogs. In each dog, two wounds were treated with HD, cemella asiatica extract (Centrasol$^{(R)}$) and normal saline, respectively. For six weeks, the wounds were evaluated grossly for contraction, epithelialization and healing and were examined histopathologically. In the first week of the wound healing period, HD stimulated wound contraction and healing more significantly than centasol and normal saline (p<0.05). Neutrophils were more increased in the HD-treated wounds than those in centasol or normal saline treated wounds. In the second week, HD stimulated epithelialization more significantly than centasol or normal saline (p<0.05), and neovascularization and granulation more increased in the HD-treated wounds than those in centasol and normal saline treated wounds. In conclusion, HD was the most effective on early wound contraction, epithelialization and healings among three experimental drugs in full-thickness skin wound.

• Korean Journal of Medicinal Crop Science
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• v.15 no.5
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• pp.311-314
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• 2007

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the most important angiogenic molecules associated with tumor-induced neovascularization. This study was carried out to investigate inhibitory effect of extracts from root of Rehmannia glutinosa LIBOSCHITZ (Rehmannia Radix and Rehmannia Radix Preparata) on endothelial cell proliferation. The methanol extracts from the medicinal herb were fractionated into n-hexane, ethyl acetate, n-butanol and aqueous fractions. Among the four fractions, the n-butanol fraction from R. Radix on exhibited highly effective inhibition (${\approx}79%$ inhibition) on the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and then ethyl acetate fraction from R. Radix (${\approx}45%$ inhibition) at the concentration of $100\;{\mu}g/ml$. The n-butanol fraction efficiently blocked the VEGF- and bFGF-induced HUVEC proliferation in a dose-dependent manner, but did not affect the growth of HT1080 human fibrosarcoma cells. The n-butanol fraction more efficiently blocked the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and VEGF- and bFGF-induced human umbilical vein endothelial cell proliferation than the fraction from R. Radix Preparata. Our results suggest that Rehmannia Radix may be used as a candidate for developing anti-angiogenic agent.