• The Journal of Internal Korean Medicine
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• v.35 no.4
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• pp.416-427
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• 2014

Objectives: The purpose of this study was to investigate the antineoplastic effect of several herbal medicine mixtures (compositions of Astragalus membranaceu, Angelica gigas, Trichosanthes kirilowii, Panax ginseng, Rhus verniciflua Stokes) on the SNU-80 anaplastic thyroid carcinoma cell line. Methods: MTT assay was used to examine whether our herbal medicine mixtures decreased cell growth rate of SNU-80. Wound healing assay and Transwell invasion assay was performed to investigate whether our herbal medicine mixtures affect the migration and invasion of anaplastic cancer cells, SNU-80. ELISA assay was performed to know if our herbal medicine mixtures suppressed the expression of pro-invasive molecules, such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) secreted from SNU-80. Results: MTT assay demonstrated that A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas :T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 strongly suppressed the growth of SNU-80. Wound healing assay demonstrated that A. membranaceus:A. gigas=3:1, A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 inhibited the migration of SNU-80. Transwell invasion assay demonstrated that A. membranaceus:A. gigas=1:1, A. membranaceus:A. gigas:T. kirilowii =1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng=1:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng :R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 inhibited the invasion of SNU-80. ELISA assay demonstrated that A. membranaceus :A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 suppressed the expression of VEGF. Also, A. membranaceus:A. gigas=1:1, A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus :A. gigas:T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes =1:1:1:1:1 or 3:1:1:1:1 suppressed the expression of MMP-2. Conclusions: The results obtained in this study suggest that several herbal medicine mixtures suppresse the growth and inhibit the migration and invasion of SNU-80, which is anaplastic thyroid cancer cells. Especially, A. membranaceus:A. gigas: T. kirilowii=1:1:1 mixture had a stronger anti-cancer effect.

• The Journal of Korean Physical Therapy
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• v.15 no.3
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• pp.16-44
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• 2003

Skeletal muscle regeneration is a vital process for various muscle myopathies and muscular adaptation to physiological overload. Angiogenesis is the key event in the process of muscle regeneration, and vascular endothelial growth factor(VEGF) plays an important role in it. The purpose of this study was to evaluate the effect of GaAlAs(830nm) laser and immunoreactivity of VEGF on angiogenesis after muscle contusion injury. Muscle contusion injury was induced in the triceps surae muscle by dropping a metal bead(31.4g). GaAlAs laser irradiation(power 20 mW, frequency 2000 Hz, treatment time 15 min) was applied directly to the skin of injured muscle daily for seven days. The experimental group I was irradiated immediately by laser after injury, whereas the experimental group II was irradiated after 1 day of injury. The control group was non-irradiated. The results of this study were as follows. 1. In morphological observation, there were no significant changes in experimental and control groups for 7 days. At 3 days, however, the splited muscle fibers were observed in experimental groups, and the muscle atrophy and granular tissue viewed at 7 days in control group. 2. The VEGF was expressed in muscle fiber that located in the interspace between gastrocnemius and soleus muscles. As the time coursed, the immunoreactivity of VEGF also seemed to be strong in the individual muscle fibers. 3. The experimental group I & II showed higher immunoreactivity of VEGF than control group(p<0.05). Then, the experimental group I showed higher than group II especially(p<0.05). These data suggest GaAlAs semiconduct diode laser irradiation(830nm) enhanced angiogenesis in the skeletal muscle induced contusion injury, and immediate laser irradiation after injury promoted the angiogenesis greatly than after 1 day of injury.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.9
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• pp.1400-1410
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• 2020

Objective: Genome-wide association study and two meta-analysis based on GWAS performed to explore the genetic mechanism underlying variation in pig number born alive (NBA) and total number born (TNB). Methods: Single trait GWAS and two meta-analysis (single-trait meta analysis and multi-trait meta analysis) were used in our study for NBA and TNB on 3,121 Yorkshires from 4 populations, including three different American Yorkshire populations (n = 2,247) and one British Yorkshire populations (n = 874). Results: The result of single trait GWAS showed that no significant associated single nucleotide polymorphisms (SNPs) were identified. Using single-trait meta analysis and multi-trait meta analysis within populations, 11 significant loci were identified associated with target traits. Spindlin 1, vascular endothelial growth factor A, forkhead box Q1, msh homeobox 1, and LHFPL tetraspan submily member 3 are five functionally plausible candidate genes for NBA and TNB. Compared to the single population GWAS, single-trait Meta analysis can improve the detection power to identify SNPs by integrating information of multiple populations. The multiple-trait analysis reduced the power to detect trait-specific loci but enhanced the power to identify the common loci across traits. Conclusion: In total, our findings identified novel genes to be validated as candidates for NBA and TNB in pigs. Also, it enabled us to enlarge population size by including multiple populations with different genetic backgrounds and increase the power of GWAS by using meta analysis.

• Journal of Life Science
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• v.24 no.12
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• pp.1345-1355
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• 2014

The interruption of angiogenesis using herbal extracts is now recognized as a useful approach for treating many solid tumors. To date, the best-validated antitumor approach is to target the vascular endothelial growth factor (VEGF)-induced angiogenic pathway. In the present study, we first identified the antiangiogenic activity of a hot-water extract of Rubus coreanus Miquel (RCMHE) in vitro and ex vivo. This extract suppressed VEGF-induced angiogenesis, the phosphorylation of extracellular regulated kinase (ERK), p38 and the activation of matrix metalloproteinases (MMPs). RCMHE also inhibited the VEGF-responsive phosphorylation of VEGFR2. These results clearly show that RCMHE may have potential therapeutic value for angiogenesis-associated human diseases through the suppression of angiogenesis and the interruption of the phosphorylation of VEGFR2.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.2
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• pp.17-34
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• 2010

Objectives : This study was carried out to know the effects of Gwanjul8-bang(here in after reffered to GJ8) on the inhibition of arthritis induced by collagen on DBA/1J mice. Methods : For this purpose, GJ8 was orally administered to mouse with arthritis induced by collagen II. Cytotoxicity, hepatotoxicity, arthritis index, value of immunocyte in draining lymph node(DLN) and paw joint, cytokine in serum were measured in vivo. Results : 1. The arthritis index was decreased significantly. 2. In total cell counts of DLN and paw joint, the cells in DLN increased significantly while there was a significant decrease in paw joint. 3. In lymph nodes, $CD19^+$, $CD3^+$, $CD4^+/CD25^+$ cells increased significantly, and $B220^+/CD23^+$ cells decreased significantly. 4. In joints, $CD3^+$, $CD4^+$, $CD11b^+/Gr-1^+$ cells decreased significantly. 5. The levels of $TNF-{\alpha}$, IL-6, IL-17, MCP-1 and vascular endothelial growth factor(VEGF) in serum was significantly decreased compared with control. 6. Anti-collagen II in serum was significantly decreased compared with control. 7. The degree of arthritis induced damage of joint of GJ8 group is slight compared with control group in histopathologic observation(hematoxylin & eosin(H&E), Masson-Trichrome(MT) staining). Conclusions : Comparison of the results for this study showed that GJ8 had immunomodulatory effects. So we expect that GJ8 should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore there seems to be many clinical research needed in the future.

• Clinics in Shoulder and Elbow
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• v.22 no.2
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• pp.79-86
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• 2019

Background: Increased oxidative stress and inflammation play a critical role in the etiopathogenesis of chronic tendinopathy. Melatonin is an endogenous molecule that exhibits antioxidant and anti-inflammatory activity. The aim of this study was to evaluate the biochemical and histopathological effects of exogenous melatonin administrations in supraspinatus overuse tendinopathy. Methods: Fifty rats were divided into the following four groups: cage activity, melatonin treatment, corticosteriod therapy, and control. Melatonin (10 mg/kg, intraperitoneal; twice a day) and triamcinolone (0.3 mg/kg, subacromial; weekly) were administered to the treatment groups after the overuse period. Biochemical and histopathological evaluations were performed on serum samples and biopsies obtained from rats. Plasma inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were evaluated biochemically. Results: The TAS, TOS, OSI, iNOS, and VEGF values were significantly lower than the pre-treatment levels in rats receiving exogenous melatonin treatment (3 or 6 weeks) (p<0.05). TOS, iNOS, VEGF, and OSI values after 3 weeks of triamcinolone administration, and TOS, VEGF, and OSI levels after 6 weeks of triamcinolone application, were significantly lower than the pre-treatment levels (p<0.05). Conclusions: Exogenous melatonin application in overuse tendinopathy reduces oxidative stress and inflammation. Melatonin might be an alternative potential molecule to corticosteroids in the treatment of chronic tendinopathy.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.181-189
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• 2024

Background: Cigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. Methods: Mice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. Results: KRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. Conclusion: Taken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.

• Childhood Kidney Diseases
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• v.14 no.2
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• pp.166-173
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• 2010

Purpose : Genetic and clinical factors can influence the permeability of the peritoneal membrane. The peritoneal equilibration test (PET) is helpful in measuring peritoneal permeability in peritoneal dialysis (PD). We investigated the influence of genetic polymorphism of vascular endothelial growth factor (VEGF) on the PET parameters. Methods : Pediatric patients who underwent PET within 12 months of initiating PD at Seoul National University Children's Hospital and Samsung Medical Center were selected. The patients with positive history of peritonitis before PET were excluded. The VEGF -2578C/A, -14978T/C, -1154G/A, -634G/C, and +936C/T single-nucleotide polymorphisms were genotyped. Results : The mean 4-hour dialysate-to-plasma ratio for creatinine (D/P creatinine) and the mean 4-hour dialysate glucose to baseline dialysate glucose ratio (D/$D_0$ glucose) were $0.56{\pm}0.13$ and $0.43{\pm}0.11$, respectively. The patients with haplotype CTGGC showed higher 4-hour D/P creatinine ($0.67{\pm}0.12$ vs $0.50{\pm}0.09$, P=0.007) and lower 4-hour D/$D_0$ glucose ($0.35{\pm}0.12$ vs $0.47{\pm}0.08$, P=0.037) than those without haplotype CTGGC. Conclusion : The VEGF genetic polymorphism may influence the peritoneal solute transport.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.191-199
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• 2005

Background: Though infections of Helicobacter pylori (H. pylori) are closely associated with activation of host angiogenesis, the underlying mechanisms, as well as the strategy for its prevention, have not been identified. Here, we investigated a causal role of H. pylori infection in angiogenesis of gastric mucosa and a potent inhibitory effect of a gastric proton pump inhibitor (PPI) on the gastropathy. Materials and Methods: A comparative analysis of CD 34 expression in tissues obtained from 20 H. pylori-associated gastritis and 18 H. pylori-negative gastritis patients was performed. Expression of $HIF-1{\alpha}$ and VEGF were tested by using RT-PCR. To evaluate the direct effect of H. pylori infection on differentiation of endothelial HUVEC cells, we carried out an in vitro angiogenesis assay. Results: H. pyfori-associated gastritis tissues showed significantly higher density of $CD34^+$ blood vessels than did H. pylori-negative gastritis tissues, and the levels were well correlated with expressions of $HIF-1{\alpha}$. Conditioned media from H. pylori-infected gastric mucosal cells stimulated a tubular formation of HUVEC cells. We also found a significant inhibitory effect of PPI, an agent frequently used for H. pylori eradication, on H. pylori-induced angiogenesis. This drug effectively inhibited the phosphorylation of MAP kinase ERK1/2, which is a principal signal for H. pylori-induced angiogenesis. Conclusion: The fact that PPls can down-regulate H. pylori-induced angiogenesis suggest that anti-angiogenic treatment using PPI may be a preventive approach for H. pylori-associated carcinogenesis.

• Journal of Korean Neurosurgical Society
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• v.40 no.6
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• pp.428-433
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• 2006

Objective : We investigated the pattern of glucose uptake in meningiomas using $^{18}F$-fluoro-2-deoxy-D-glucose[FDG] PET/CT. It was hypothesized that the degree of glucose uptake in each tumor could predict the histologic grade. Methods : In 19 patients with meningiomas, the Ki-67 proliferative index, standardized uptake values[SUV] of FDG uptake, tumor to contralateral gray matter ratio[TGR] of SUV, tumor size, edema grade, vascular endothelial growth factor[VEGF] expression, histopathologic grade and the blood supply pattern were assessed. Results : Of the 19 meningiomas, 8 were meningothelial, 1 fibrous, 2 transitional, 1 psammomatous, 2 angiomatous, and 5 atypical. The tumor proliferative index of Ki-67, tumor size, and peritumoral edema were larger in the histopathologic grade-2 meninigiomas than in the grade-1 meningioma group. There were no significant differences in SUV and TGR between two groups. Tumor size and peritumoral edema were significantly larger in VEGF-positive tumors than in negative tumors. Conventional angiography was performed in 12 patients. Dural supply was noted predominantly in 2 patients. Four patients had mainly pial cortical supply patterns. In tumors with more pial supply, VEGF was more frequently positive. There was a significant relation between SUV and Ki-67 and between SUV and peritumoral edema. Conclusion : We found FOG uptake in meningiomas is associated with proliferative potential, however, no clear limits of SUV and TGR can be set to distinguish between grade-1 and grade-2 meningiomas, which makes the assessment of malignancy grade using PET scan metabolic imaging difficult in individual cases.