• Journal of The Korean Dental Society of Anesthesiology
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• v.14 no.2
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• pp.107-114
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• 2014

Background: Angiogenesis has been recognized an essential precondition for osteogenesis. Because reduction and disruption of the blood supply to tissue cause tissue hypoxia, pathological bone loss affected by hypoxia often can occur in various clinical conditions. The effects of propofol on the process of osteogenesis have received little direct attention. Therefore, we investigated the effect of propofol on the growth and function of osteoblasts under hypoxic condition. Methods: After propofol (3, 30, $300{\mu}M$) preconditioning for 2 hours, hFOB 1.19 human osteoblast cells were cultured under 1 % oxygen tension for 48 hours. Using real time PCR and western blot analysis, we analyzed the expression of, BMP-2, TGF-${\beta}1$, type I collagen, osteocalcin, HIF-1s and Akt. Cell viability was also determined by MTT assay. Results: Propofol preconditioning on hypoxic-cultured osteoblast promoted the expressions of BMP-2, TGF-${\beta}1$, type I collagen and osteocalcin and induced hypoxia-mediated HIF-1 activation and the expression of Akt protein. Propofol with $300{\mu}M$ significant decreased cell viability compared to control. Conclusions: Clinically relevant concentrations of propofol are not cytotoxic to hypoxic osteoblasts in vitro. Propofol preconditioning on hypoxic-cultured osteoblast stimulates proliferation and differentiation of osteoblast through induced expression of BMP-2, TGF-${\beta}1$, type I collagen and osteocalcin. Propofol might promote angiogenesis and bone regeneration under hypoxic condition.

• Journal of Radiation Industry
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• v.9 no.4
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• pp.187-192
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• 2015

CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrix interactions. In particular, splice variants of CD44 are particularly overexpressed in a large number of malignancies and carcinomas. In this study, the $^{177}Lu$-labelled CD44 targeting antibody was prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with the equivalent molar ratio of cysteine-based DTPA-NCS and radioimmunoconjugated with $^{177}Lu$ at room temperature within 15 minutes. The stability was tested in human serum. An in vitro study was carried out in HT-29 human colon cancer cell lines. For the biodistribution study $^{177}Lu$-labelled anti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteine-based DTPA-NCS and purified by a centricon filter system having a molecular cut-off of 50 kDa. Radioimmunoconjugation with $^{177}Lu$ was reacted for 15 min at room temperature. The radiolabeling yield was >99%, and it was stable in human serum without any fragmentation or degradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cell surfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was 43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. The anti-CD44 monoclonal antibody for the targeting of colon cancer was effectively radioimmunoconjugated with $^{177}Lu$. The in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell binding assay. In addition, the antibody's tumor targeting ability was demonstrated with very high uptake in tumors. This radioimmunoconjugate is applicable to therapy in human colon cancer with highly expressed CD44.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.12
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• pp.1889-1896
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• 2019

Objective: This study aimed to investigate the effects of prepartum body condition score (BCS) on the milk yield, lipid metabolism, and oxidative status of Holstein cows. Methods: A total of 112 multiparous Holstein cows were divided into 4 groups according to the BCS at 21 days before calving: medium BCS (3.0 to 3.25, MBCS), high BCS (3.5 to 3.75, HBCS), higher BCS (4.0 to 4.25, HerBCS), and highest BCS (4.5 to 5.0, HestBCS). Blood samples were collected on 21, 14, and 7 days before calving (precalving), on the calving day (calving), and on 7, 14, and 21 days after calving (postcalving). The indices of lipid metabolism and oxidative status were analyzed using bovine-specific enzyme-linked immunosorbent assay kit. Colostrum were taken after calving and analyzed by a refractometer and milk analyzer. The individual milk yield was recorded every 3 days. Results: The density and levels of immune globulin and lactoprotein of colostrum from Holstein cows in the HestBCS group were the highest (p<0.05). These animals not only had the highest (p<0.05) levels of serum non-esterified fatty acids and beta-hydroxybutyrate, but also had the highest (p<0.05) levels of malondialdehyde, superoxide dismutase, catalase, vitamin A, and vitamin E. In addition, greater (p<0.05) BCS loss was observed in the HestBCS cows. Conclusion: This study demonstrates that the milk yield, lipid metabolism, and oxidative status of Holstein cows are related to prepartum BCS and BCS loss during the transition period. HestBCS cows are more sensitive to oxidative stress and suffer greater loss of BCS after calving, whereas the MBCS animals had better milk yield performance.

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.806-810
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• 2004

Metformin is a biguanide antihyperglycemic agent often used for the treatment of non-insulin dependent diabetics (NIDDM). In this study, the pharmacokinetics and pharmacodynamics of metformin were investigated in Korean healthy volunteers during a fasting state for over 10 h. In order to evaluate the amount of glucose-lowering effect of metformin, the plasma concentrations of glucose were measured for a period of 10 h followed by the administration of metformin (oral 500 mg) or placebo. In addition, the concentration of metformin in blood samples was determined by HPLC assay for the drug. All volunteers were consumed with 12 g of white sugar 10 minutes after drug intake to maintain initial plasma glucose concentration. The time courses of the plasma concentration of metformin and the glucose-lowering effect were analyzed by nonlinear regression analysis. The estimated $C_{max}$, $T_{max}$, $CL_{t}$/F (apparent clearance), V/F(apparent volume of distribution), and half-life of metformin were 1.42$\{pm}$0.07 $\mu\textrm{g}$/mL, 2.59$\{pm}$0.18h, 66.12$\{pm}$4.6 L/h, 26.63 L, and 1.54 h respectively. Since a significant counterclock-wise hysteresis was found for the metformin concentration in the plasma-effect relationship, indirect response model was used to evaluate pharmacodynamic parameters for metformin. The mean concentration at half-maximum inhibition $IC_{50}$, $k_{in}$, $k_{out}$ were 2.26 $\mu\textrm{g}$/mL, 83.26 $H^{-1}$, and 0.68 $H^{-1}$, respectively. Therefore, the pharmacokinetic-pharmacodynamic model may be useful in the description for the relationship between plasma concentration of metformin and its glucose-lowering effect.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.3
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• pp.245-254
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• 2021

Objective: In humans, polycystic ovary syndrome (PCOS) is an androgen-dependent ovarian disorder. Aberrant gene expression in folliculogenesis can arrest the transition of preantral to antral follicles, leading to PCOS. We explored the possible role of altered gene expression in preantral follicles of estradiol valerate (EV) induced polycystic ovaries (PCO) in a mouse model. Methods: Twenty female balb/c mice (8 weeks, 20.0±1.5 g) were grouped into control and PCO groups. PCO was induced by intramuscular EV injection. After 8 weeks, the animals were killed by cervical dislocation. Blood serum (for hormonal assessments using the enzyme-linked immunosorbent assay technique) was aspirated, and ovaries (the right ovary for histological examinations and the left for quantitative real-time polymerase) were dissected. Results: Compared to the control group, the PCO group showed significantly lower values for the mean body weight, number of preantral and antral follicles, serum levels of estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone, and gene expression of TGFB1, GDF9 and BMPR2 (p<0.05). Serum progesterone levels were significantly higher in the PCO animals than in the control group (p<0.05). No significant between-group differences (p>0.05) were found in BMP6 or BMP15 expression. Conclusion: In animals with EV-induced PCO, the preantral follicles did not develop into antral follicles. In this mouse model, the gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which is probably related to the pathologic conditions of PCO. Hypoandrogenism was also detected in this EV-induced murine PCO model.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.4
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• pp.368-373
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• 2021

Objective: In this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes. Methods: A prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses. Results: In the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients. Conclusion: Baseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS. This possibility should be confirmed in further research.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.122-122
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• 2019

Protaetia brevitarsis (PB) extracts has been traditionally used as medicinal stuff to treat blood stasis, occlusion of menstruation, tetanus and liver cancer in Asian countries (Korea, Japan, China, Taiwan, India and Myanmar). Especially, Donguibogam, which is traditional korean medicinal book, described the PB extracts as traditional medicine to treat hepatic diseases and vascular disorders. The PB extracts has been considered as highly nutritional food. The major constituents of PB extracts are rich in protein, healthy fats, iron, calcium. Recent studies announced that PB extracts has hepatoprotective effect and anti-microbacterial effect. However, the effect of PB on ulcerative colitis has not been uncovered yet. The aim of this study was to examine the anti-inflammatory effect of PB extracts in dextran sulfate sodium (DSS)-induced colitis mice model. Cytotoxicity of PB was determined by MTT assay and the antiinflammatory effect of PB extract was investigated by measuring nitric oxide (NO) production. PB extracts did not show any cytotoxicity. AIso, PB extracts supressed NO production in LPS-stimulated mice peritoneal macrophages. To determine whether PB could be an effective treatment on ulcerative colitis, DSS was administered in BALB/c mice for 10 days. PB extract significantly improved the clinical signs of DSS-induced UC, including body weight loss, colon length shortening, and disease activity index increase, with histological markers of colon injury. These findings indicated the possibility of PB as a therapeutic agent on ulcerative colitis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.2
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• pp.109-115
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• 2019

Aster Yomena (AY) has been used in traditional medicine to treat diseases such as obesity, hyperlipidemia, atherosclerosis, diabetes and osteoarthritis. However, protective effect of AY on acute pancreatitis (AP) has not been reported. The present study examined the anti-inflammatory effects of an ethanol extract of AY on cerulein-induced AP. AP was induced in mice by intraperitoneally injecting cerulein ($50{\mu}g/kg$) hourly for 6 times. 70% ethanol extract of AY (0.1, 0.2, and 0.5 g/kg) was orally administered for 1 week before acute pancreatitis induction. The mouse was killed at 6 hours after the final cerulein injection. The pancreas and lung were rapidly removed for histological examination and myeloperoxidase (MPO) assay. Blood samples were taken to determine serum amylase and lipase activity. In addition real-time reverse transcription-polymerase chain reaction (RT-PCR) was also performed to investigate mRNA expression of proinflammatory cytokines such as $TNF-{\alpha}$. $IL-1{\beta}$, and IL-6. Administration of AY significantly ameliorated pancreatic weight to body weight ratio, histological damages and MPO activity during AP. In addition, AY inhibited the serum amylase and lipase activity during AP. Also, mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 were inhibited by AY against AP. Our results revealed that pre-treatment of AY reduces the severity of cerulein-induced AP. Therefore, AY may have a protective effect drug against AP.

• Clinical and Experimental Reproductive Medicine
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• v.46 no.3
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• pp.132-139
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• 2019

Objective: Vitamin D-binding protein (VDBP) mediates various biological processes in humans. The goal of this study was to investigate whether VDBP gene polymorphisms could predispose Korean women to endometriosis. Methods: We prospectively enrolled women with endometriosis (n = 16) and healthy controls (n = 16). Total serum 25-hydroxyl vitamin D (25(OH)D) concentrations were measured using an Elecsys vitamin D total kit. Levels of bioavailable and free 25(OH)D were calculated. Concentrations of VDBP were measured using a vitamin D BP Quantikine ELISA kit. DNA was extracted using a DNeasy blood & tissue kit. Two single-nucleotide polymorphisms (SNPs; rs4588 and rs7041) in GC, the gene that codes for VDBP, were analyzed using a TaqMan SNP genotyping assay kit. The functional variant of VDBP was determined based on the results of the two SNPs. Results: Gravidity and parity were significantly lower in the endometriosis patients than in the control group, but serum CA-125 levels and the erythrocyte sedimentation rate were significantly higher. Total serum 25(OH)D levels in the endometriosis patients were significantly lower than in the control group. However, serum bioavailable 25(OH)D, free 25(OH)D, and VDBP levels did not differ significantly between the endometriosis and control groups. The genotypes and allele frequencies of GC were similar in both groups. Conclusion: Korean women with endometriosis had lower total serum 25(OH)D concentrations than controls. Neither serum VDBP concentrations nor polymorphisms in the gene coding for VDBP were associated with endometriosis. Further studies are needed to investigate the pathophysiology and clinical implications of 25(OH)D and VDBP in endometriosis.

• Journal of Periodontal and Implant Science
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• v.48 no.6
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• pp.337-346
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• 2018

Purpose: Peripheral artery disease (PAD) is a form of arteriosclerosis that occurs in the extremities and involves ischemia. Previous studies have reported that patients with periodontitis are at high risk for PAD. However, the relationship between these 2 diseases has not yet been fully elucidated. In this cross-sectional study, we investigated this relationship by comparing patients with PAD to those with arrhythmia (ARR) as a control group. Methods: A large-scale survey was conducted of patients with cardiovascular disease who visited Tokyo Medical and Dental University Hospital. We investigated their oral condition and dental clinical measurements, including probing pocket depth, bleeding on probing, clinical attachment level, and number of missing teeth; we also collected salivary and subgingival plaque samples and peripheral blood samples. All patients with PAD were extracted from the whole population (n=25), and a matching number of patients with ARR were extracted (n=25). Simultaneously, ARR patients were matched to PAD patients in terms of age, gender, prevalence of diabetes, hypertension, dyslipidemia, obesity, and the smoking rate (n=25 in both groups). Real-time polymerase chain reaction was performed to measure the bacterial counts, while the enzyme-linked immunosorbent assay method was used to measure anti-bacterial antibody titers and proinflammatory cytokine levels in serum. Results: PAD patients had more missing teeth ($18.4{\pm}2.0$) and higher serum levels of C-reactive protein ($1.57{\pm}0.85mg/dL$) and tumor necrosis factor-alpha ($70.3{\pm}5.7pg/mL$) than ARR patients ($12.0{\pm}1.7$, $0.38{\pm}0.21mg/dL$, and $39.3{\pm}4.5pg/mL$, respectively). Meanwhile, no statistically significant differences were found in other dental clinical measurements, bacterial antibody titers, or bacterial counts between the 2 groups. Conclusions: Our findings suggested that PAD patients had poorer oral and periodontal state with enhanced systemic inflammation.