• Molecules and Cells
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• v.42 no.9
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• pp.661-671
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• 2019

Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising for regenerating degenerated intervertebral discs (IVDs), but the low efficiency of nucleus pulposus (NP)-specific differentiation limits their clinical applications. The Sonic hedgehog (Shh) signaling pathway is important in NP-specific differentiation of ADSCs, and Smoothened Agonist (SAG) is a highly specific and effective agonist of Shh signaling. In this study, we proposed a new differentiation strategy with the use of the small molecule SAG. The NP-specific differentiation and extracellular matrix (ECM) synthesis of ADSCs were measured in vitro, and the regenerative effects of SAG pretreated ADSCs in degenerated IVDs were verified in vivo. The results showed that the combination of SAG and transforming growth factor-${\beta}3$ ($TGF-{\beta}3$) is able to increase the ECM synthesis of ADSCs. In addition, the gene and protein expression levels of NP-specific markers were increased by treatment with SAG and $TGF-{\beta}3$. Furthermore, SAG pretreated ADSCs can also improve the disc height, water content, ECM content, and structure of degenerated IVDs in vivo. Our new differentiation scheme has high efficiency in inducing NP-specific differentiation of ADSCs and is promising for stem cell-based treatment of degenerated IVDs.

• YAKHAK HOEJI
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• v.51 no.6
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• pp.402-408
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• 2007

The aim of this study was to evaluate the effect of menstration among the influencing factors for the GnRH agonist (as G: depot goserelin 3.6 mg) therapy prior to the planned myomectomy for women who wanted to preserve their fertility. We reviewed total 48 patients. with the G therapy prior to the planned myomectomy from August 1st, 2005 to August 31st, 2006. The patients were classified by the G group (n=28) and the immediate surgery (as S) group (n=20). The G group (n=19) underwent the G therapy for 3 month courses, and then the efficacy was evaluated by menstruation and the myoma volumes. In the G group (n=19), therapy was effective, and the mean age was $32.4{\pm}6.5$ years. After the completion of G therapy, the mean volume of the myoma by ultrasonography was reduced to $85.2{\pm}71.2cm^3$ comparing of $430.6{\pm}248.8cm^3$ at first visit. The 11 patients had menstruation and the rest 8 patients with amenorrhea had less reduced volume of the myoma ($124.05{\pm}79.85cm^3\;v.s.\;329.41{\pm}234.0cm^3$ p<0.05). In the immediate S group, the myoma volumes by sonography was also checked for accuracy (${\alpha}=1.0$). As the result, the initial myoma volume had the positive correlations to the effectiveness with G therapy. However, the occurrence and frequency of the menstruation during the G therapy had a negative correlation. In conclusion, the use of G prior to the planned myomectomy was effective in reducing myoma volume and the menstruation.

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2006.05a
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• pp.439-440
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• 2006

This research proposes a novel method of shape display to present 3-dimensional objects. Shape displays allow us to feel the actual volume of the object, unlike conventional 2D visual displays of 3D objects. The proposed method employs a wire frame structure to present 3D objects. The wire frame is composed of small units driven by shape memory alloy(SMA) actuators. The drive unit is analogous to the agonist-antagonist system of animal musculoskeletal systems, where the SMA actuators serve as agonist and antagonist muscles. The force in the SMA actuator is controlled by electrical current. The drive unit is equipped with the locking mechanism so that it can sustain the external force exerted by the user as well as the own weight of the wire frame structure. By controlling the current into the SMA actuator and locking mechanism, we call control the angle of the drive unit. A chain of drive units enables presentation of 2 dimensional objects. 3 dimensional presentations are possible by collecting the chains of drive units.

• Molecules and Cells
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• v.25 no.1
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• pp.91-98
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• 2008

The Glu/$Asp^{7.32}$ residue in extracellular loop 3 of the mammalian type-I gonadotropin-releasing hormone receptor (GnRHR) interacts with $Arg^8$ of GnRH-I, conferring preferential ligand selectivity for GnRH-I over GnRH-II. Previously, we demonstrated that the residues (Ser and Pro) flanking Glu/$Asp^{7.32}$ also play a role in the differential agonist selectivity of mammalian and non-mammalian GnRHRs. In this study, we examined the differential antagonist selectivity of wild type and mutant GnRHRs in which the Ser and Pro residues were changed. Cetrorelix, a GnRH-I antagonist, and Trptorelix-2, a GnRH-II antagonist, exhibited high selectivity for mammalian type-I and non-mammalian GnRHRs, respectively. The inhibitory activities of the antagonists were dependent on agonist concentration and subtype. Rat GnRHR in which the Ser-Glu-Pro (SEP) motif was changed to Pro-Glu-Val (PEV) or Pro-Glu-Ser (PES) had increased sensitivity to Trptorelix-2 but decreased sensitivity to Cetrorelix. Mutant bullfrog GnRHR-1 with the SEP motif had the reverse antagonist selectivity, with reduced sensitivity to Trptorelix-2 but increased sensitivity to Cetrorelix. These findings indicate that the residues flanking $Glu^{7.32}$ are important for antagonist as well as agonist selectivity.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.400-404
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• 2006

This study examined the effect of Gamma-Amino butyric acid (GABA) and selective GABA receptor related drugs on the electrically stimulated relaxation in the lower esophageal sphincter muscle (LES) of a cat. Tetrodotoxin $(10^{-6}\;M)$ suppressed the electrically stimulated (0.5-5 Hz) relaxation of the LES. However, guanethidine $(10^{-6}\;M)$ and atropine $(10^{-6}\;M)$ had no effect indicating that the relaxations were neurally mediated via the nonadrenergic and noncholinergic (NANC) pathways. NG-nitro-L-arginine methyl ester ($10^{-4}M$, L-NAME) also inhibited the relaxant response but did not completely abolish the electrically stimulated relaxation with 60% inhibition, which suggests the involvement of nitric oxide as an inhibitory transmitter. This study examined the role of GABA, an inhibitory neurotransmitter, on neurally mediated LES relaxation. GABA ($10^{-3}-10^{-5}M$, non selective receptor agonist), muscimol ($10^{-3}-10^{-5}M$, GABA-A agonist), and baclofen ($10^{-3}-10^{-5}M$, GABA-B agonist) had no significant effect on the electrically stimulated relaxation. Moreover, bicuculline ($10^{-5}M$, GABA-A antagonist) and phaclofen ($10^{-5}M$, GABA-B antagonist) had no inhibitory effect on the electrically stimulated relaxation. This suggests that GABA and the GABA receptor are not involved in the electrically stimulated NANC relaxation in the cat LES.

• Korean Journal of Plant Resources
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• v.25 no.6
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• pp.670-681
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• 2012

Herb extracts commercially used in Korea were screened for PPAR-${\gamma}$ agonist test and ${\alpha}$-glucosidase inhibition assay. Total 16 herb plants had a PPAR-${\gamma}$ agonist activity. Specially, Alisma orientale Juz (108.41%), Ephedra sinica (98.22%), Sasa japonica Makino var. purpurascens Nakai (140.68%), Astragalus membranaceus Bunge (106.79%) and Cnidium officinale Makino (113.00%) showed high PPAR-${\gamma}$ agonist activity rate compared with rosiglitazone's (167.46%). And Cornus officinalis S. et Z. (90.3%), Cinnamomum cassia Blume (89.2%), Psoralea corylifolia L. (89.8%), Paeonia japonica (Makino) Miyabe (92.4%) and Paeonia suffruticosa Andr (93.2%), showed high ${\alpha}$-glucosidase inhibition rates. These results support previous reports of the efficacy of Oriental medicinal plants used for diabetes mellitus.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.3
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• pp.389-398
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• 1999

Objective: This study was designed to evaluate the effects of endogenous LH surge, GnRH agonist (GnRH-a) or human chorionic gonadotropin (hCG) as ovulation trigger on pregnancy rate by intrauterine insemination (IUI). Method: Patients received daily 100 mg of clomiphene citrate (CC) for 5 days starting on the third day of the menstrual cycle followed by human menopausal gonadotropin (hMG) for ovulation induction. Follicles larger than >16 mm in diameter were present in the ovary, frequent LH tests in urine were introduced to detect an endogenous LH surge. Final follicular maturation and ovulation were induced by GnRH-a 0.1 mg (s.c.) or hCG $5,000{\sim}10,000$ IU (i.m.) administration except natural ovulation. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. Results: There were no differences in age, duration of infertility and follicle size, but more ampules of hMG were used in GnRH-a group compared to hCG 10,000 IU treated group (p<0.05). Lower level of estradiol ($E_2$) on the day of hCG or GnRH-a injection was observed in hCG 10,000 IU group than other treatment groups (p<0.01). The overall clinical pregnancy rate was 19.8% per cycle (32/162) and 22.2% per patient (32/144). Pregnancy rate was higher in natural-endogenous LH surge group (37.5%, 9/24) than GnRH-a (18.8%) or hCG treated group (20.9% & 13.9%), but this difference was not statistically significant. No patient developed ovarian hyperstimulation. Abortion rate was 22.2% (2/9) in hCG 5,000 IU group. Delivery or ongoing pregnancy rate was 37.5% (9/24), 18.8% (3/16), 16.3% (7/43) and 13.9% (11/79) in endogenous LH surge, GnRH-a, hCG 5,000 IU and hCG 10,000 IU treatment groups, respectively. Conclusion: These results support the concept that use of natural-endogenous LH surge in stimulated cycles may be more effective to obtain pregnancies by IUI than GnRH-a or hCG administration.

• Clinical and Experimental Reproductive Medicine
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• v.39 no.1
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• pp.33-39
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• 2012

Objective: We devised a novel strategy, a GnRH antagonist protocol with a GnRH agonist trigger followed by frozen-thawed blastocyst transfers with long zona dissection (LZD). The purpose of this study was to investigate the clinical outcomes of this new strategy according to age. Methods: Ninety women aged less than 35 (group A) and 32 women aged 35 to 39 (group B) underwent the GnRH antagonist protocol with a GnRH agonist trigger in order to obtain many oocytes and prevent early-onset ovarian hyperstimulation syndrome (OHSS). All oocytes were cultured to the blastocyst stage and all blastocysts grade 3BB or better were cryopreserved. Embryo transfers were only performed in freeze-thaw cycles to prevent late-onset OHSS and to overcome embryo-endometrium dyssynchrony. LZD was performed just after thawing to improve hatching and implantation rates. Results: The average numbers of retrieved oocytes and blastocysts grade 3BB or better were $12.8{\pm}5.5$ and $4.4{\pm}2.6$ in group A and $10.9{\pm}7.4$ and $2.5{\pm}2.2$ in group B, respectively, and OHSS did not occur in any of the women. Implantation rates were 46.7% in group A and 39.3% in group B. Cumulative clinical pregnancy rates per retrieval were 77.8% in group A and 62.5% in group B. Cumulative ongoing pregnancy rates per retrieval were 71.1% in group A and 53.1% in group B. Conclusion: GnRH antagonist protocol with GnRH agonist trigger followed by frozen-thawed blastocyst transfers with LZD can generate many blastocysts without OHSS and maximize cumulative pregnancy rates per retrieval. This strategy is more effective in young women aged less than 35 than in women aged 35 to 39.

• YAKHAK HOEJI
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• v.52 no.1
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• pp.20-26
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• 2008

2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. Selenium was reported to have an improved antioxidant ability and to reduce the loss of dopamine. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine agonist with low neurotoxocity. In order to develop a novel dopamine agonist, we tried to synthesize the selenazoloaminoindan derivative that is a hybrid structure of aminoindan and aminoselenazole instead of aminothiazole. 2-Indanone-2-oxime was reduced with $TiCl_4$ and $NaBH_4$ to form 2-aminoindan, which was reacted with propionyl chloride to give 2-N-n-propionylaminoindan (2). Compound 2 was reduced with $TiCl_4$ and $NaBH_4$ to afford 2-N-n-propylaminoindan (3) and it was nitrated and reduced to form 5-amino-2-N-n-propylaminoindan (5), which was reacted with KSeCN, $Br_2$, and glacial acetic acid to give 4,6-dibromo-5- amino-2-N-n-propylaminoindan (7) instead of selenazole ring formation. Otherwise, compound 2 was nitrated and hydrogenated to form 5-amino-2-N-n-propionylaminoindan (9), which was treated with KSeCN, $Br_2$, and glacial acetic acid to give 4,6-dibromo-5-amino-2-N-n-propionylaminoindan (10). Compound 9 was cyc1ized with KSeCN and glacial acetic acid in the absence of $Br_2$ to give 6-amino-2-N-(n-propionylamino)selenazolo[4,5-f]indan (11).

• Journal of Veterinary Science
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• v.24 no.3
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• pp.37.1-37.14
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• 2023

Background: Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. Objectives: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). Methods: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination. The mRNA expression of interferon gamma (IFN-γ), interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-12p40, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) was determined using real-time polymerase chain reaction. Results: The combination of MPL and Poly I:C significantly upregulated immunomodulatory responses in equine cells/ without cytotoxicity. The combination induced greater mRNA expression of pro-inflammatory cytokines IFN-γ and IL-6 than MPL or Poly I:C stimulation alone in PBMCs. In addition, the combination induced significantly higher mRNA expression of IL-1β, IL-6, and IL-12p40 in MoDCs, and IL-8, MCP-1, and VEGF in BM-MSCs compared to stimulation with a single TLR agonist. Conclusions: The combination of MPL and Poly I:C can be used as a potential adjuvant candidate for vaccines to aid in preventing infectious diseases in horses.