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Fludarabine Ameliorates Lupus Nephritis by Inhibiting T Cell Infiltration through STAT1 in R848-induced Mice Models (플루다라빈을 이용한 STAT1 신호전달 조절을 통해 R848로 유도된 루푸스 동물모델 치료 효과 검증 연구)

  • Se Gwang JANG
    • Korean Journal of Clinical Laboratory Science
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    • v.56 no.3
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    • pp.207-216
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    • 2024
  • Systemic lupus erythematosus (SLE) is a systemic autoimmune disease caused by both genetic and environmental factors. Fludarabine is a selective inhibitor of signal transducer and activator of transcription 1 (STAT1). Recently, STAT1 inhibitors have been considered potential treatments for SLE, due to the relationship between its pathogenesis and STAT1 pathway-mediated cytokines such as interferons. In the current study, we evaluated the therapeutic effects of fludarabine in an SLE animal model and explored its effects on T cell responses. 12-week-old C57BL/6 mice with topically administered R848 exhibited lupus-like phenotypes. Disease activity, such as proteinuria, autoantibody levels, immunoglobulin titers, the histological score, and C3 deposition, greatly improved with fludarabine treatment. In addition, fludarabine inhibited CD4+ T cells and T helper 1 (Th1) cells in the spleen and significantly decreased the differentiation of Th1 cells in vitro. These results indicate that Th1 cells play a critical role in the pathogenesis of lupus nephritis (LN). Thus, fludarabine exerted therapeutic effects on lupus animal models by suppressing Th1 cells via STAT1 inhibition. We propose that targeting STAT1 signaling using fludarabine could be an effective therapy for treating LN.

Chemo-Mechanical Analysis of Bifunctional Linear DGEBA/Linear Amine (DDM, DDS) Resin Casting Systems (DGEBA/방향족 아민(DDM, DDS) 경화제의 벤젠링 사이의 관능기 변화가 물성 변화에 미치는 영향에 대한 연구)

  • 명인호;정인재;이재락
    • Composites Research
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    • v.12 no.4
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    • pp.71-78
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    • 1999
  • To determine the effect of chemical structure of linear amine curing agents on thermal and mechanical properties, standard epoxy resin DGEBA was cured with diaminodiphenyl methane (DDM), diaminodiphenyl sulphone (DDS) in a stoichiometrically equivalent ratio. From this work, the effect of aromatic amine curing agents. In contrast, the results show that the DGEBA/DDS cure system having the sulfone structure between the benzene rings had higher values in the conversion of epoxide, density, shrinkage (%), glass transition temperature, tensile modulus and strength, flexural modulus and strength than the DGEBA/DDM cure system having methylene structure between the benzene rings, whereas the DGEBA/DDM cure system presented higher values in the maximum exothermic temperature, thermal expansion coefficient, and thermal stability. These results are caused by the relative effects of sulfone group having strong electronegativity and methylene group having (+) repulsive property and stem from the effect of the conversion ratio of epoxide group. The result of fractography shows that the each grain size of the DDM/DGEBA system with feather-like structure is larger than that of the DDS/DGEBA system.

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Expression of Nesfatin-1/NUCB2 and Its Binding Site in Mouse Ovary (생쥐 난소 내 Nesfatin-1/NUCB2 발현과 결합 부위 확인)

  • Kim, Jin-Hee;Youn, Mi-Ra;Bang, So-Young;Sim, Ji-Yeon;Kang, Hee-Rae;Yang, Hyun-Won
    • Development and Reproduction
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    • v.14 no.4
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    • pp.287-295
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    • 2010
  • It was recently reported that nesfatin-1/NUCB2, which is secreted from the brain, controls appetite and energy metabolism. The purpose of this research was to confirm whether or not the protein and its binding site should have been expressed in the mouse reproductive organs and to know the possible effects of nesfatin-1 on the reproductive function. Using the ICR female mouse ovary and uterus, the expression of NUCB2 mRNA was confirmed with the conventional PCR and the relative amount of NUCB2 mRNA in the tissues was analyzed with real-time PCR. Immunohistochemical staining was performed using the nesfatin-1 antibody to investigate the nesfatin-1 protein expression and the biotin conjugated nesfatin-1 to confirm the binding site for nesfatin-1 in the ovary. Furthermore, in order to examine if the expression of NUCB2 mRNA in the ovary and uterus is affected by gonadotropin, its mRNA expression was analyzed after PMSG administration into mice. As a result, the expression level of NUCB2 mRNA in the ovary and the uterus was as much as the expression level in hypothalamus. As a result of the immunohistochemical staining, nesfatin-1 proteins were localized at the theca cells, the interstitial cells, and some of the luteal cells. However, the granulosa cells in the follicles did not stain. Interestingly, the oocytes in the some follicles were stained with nesfatin-1. On the other hand, nesfatin-1 protein binding sites were displayed at the theca cells and the interstitial cells near the tunica albuginea. After PMSG administration the expression level of NUCB2 mRNA was increased in the ovary and the uterus. These results demonstrate that for the first time the nesfatin-1 and its binding site were expressed in the ovary and NUCB2 mRNA expression was controlled by gonadotropin, suggesting an important role in the reproductive organs as a local regulator. Therefore, further study is needed to elucidate the functions of nesfatin-1 on the reproductive organs.

Regulation of Luteinizing Hormone Release and Subunit mRNA by GnRH and Ovarian Steroids in Cultured Anterior Pituitary Cells (흰쥐 뇌하수체전엽 배양세포에서 GnRH 및 난소호르몬에 의한 $LH{\beta}$ subunit 유전자 발현 조절에 관한 연구)

  • Kim, Chang-Mee;Park, Il-Sun;Ryu, Kyung-Za
    • The Korean Journal of Pharmacology
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    • v.30 no.1
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    • pp.19-28
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    • 1994
  • The effects of gonadoropin-releasing hormone (GnRH) and ovarian steroid hormones on the release of luteinizing hormone (LH) and its subunit mRNA levels were investigated in anterior pituitary cells in culture. LH concentration was measured by a specific radioimmunoassay and mRNA levels of u and $LH{\beta}$ subunits by RNA slot blot hybridization assay. GnRH stimulated LH release in a dose-dependent manner from cultured pituitary cells. However, the basal LH release in the absence of GnRH was not changed during the course of 24h culture, strongly suggesting that release of LH is directly controlled by GnRH. The treatment of the pituitary cells with GnRH increased $LH{\beta}$ subunit mRNA levels in a dose-dependent manner, reaching the maximum with $2\;{\times}\;10^{-10}M$ GnRH while no significant increase in ${\alpha}$ subunit mRNA levels was observed after GnRH treatment. Estradiol did not augment GnRH-induced LH release while progesterone augmented GnRH-induced LH release in a dose-dependent manner at the level of pituitary. However, estradiol and progesterone increased basal and GnRH-induced $LH{\beta}$ subunit mRNA levels in a dose-dependent manner. The treatment of estrogen antagonist, LYI17018 blocked the effect of estradiol on GnRH-induced $LH{\beta}$ subunit mRNA levels in a dose-dependent manner while progesterone antagonist, Ru486 tended to block the effect of progesterone on GnRH-induced $LH{\beta}$ subunit mRNA levels. It is therefore suggested that GnRH Playa a major role in LH release and subunit biosynthesis by influencing the steady state $LH{\beta}$ subunit mRNA loves and ovarian steroid hormones modulate subunit biosynthesis via directly acting on pituitary gonadotropes.

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Inhibition of Type II Diabetes in ob/ob Mice and Enhancement of Mitochodrial Biogenesis in C2C12 Myotubes by Korean Mistletoe Extract (한국산 겨우살이 추출물(KME)의 2형 당뇨 억제 및 근육세포 미토콘드리아 생성 증가 효과)

  • Jung, Hoe-Yune;Yoo, Yung Choon;Kim, Inbo;Sung, Nak Yun;Choi, Ok-Byung;Choi, Bo-Hwa;Kim, Jong-Bae
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.3
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    • pp.324-330
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    • 2015
  • In this study, the anti-diabetic activity of a cold water extract of Korean mistletoe (KME) was investigated in C57BL/6J Lep ob (ob/ob) mice. Oral administration of KME (50 or 100 mg/kg/d) significantly inhibited the level of blood glucose of ob/ob mice after 5 days from the beginning of KME treatment. And the anti-diabetic effect of KME was stabilized 10 days after oral administration, showing a substantial reduction of blood glucose levels by more than 20% as compared with control mice. The results of oral glucose tolerance test (OGTT) revealed that oral administration of KME gave rise to a remarkable improvement in overall glucose response. Oral administration of KME in ob/ob diabetic mice also significantly reduced blood total cholesterol (TCHO) and triglyceride (TG) levels compared with the diabetic control mice. Moreover, in an in vitro experiment using C2C12 myotubes, treatment of KME prominently increased glucose uptake. Interestingly, KME significantly increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-${\alpha}$ ($PGC-1{\alpha}$), a head regulator of mitochondrial biogenesis and oxidative metabolism, and $PGC-1{\alpha}$-associated genes such as glucose transporter type 4 (GLUT4), estrogen-related receptor-${\alpha}$ ($ERR-{\alpha}$), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TmfA) in C2C12 cells. These results suggest that KME has potential as a novel therapeutic agent for diabetes, and its anti-diabetic activity may be related to the regulation of mitochondrial biogenesis.

GATA-3 is a Key Factor for Th1/Th2 Balance Regulation by Myristicin in a Murine Model of Asthma (Myristicin이 Ovalbumin으로 유도한 천식 생쥐모델에서 Th1/Th2 Balance를 조절하는 GATA-3에 미치는 효과)

  • Lee, Kyu;Lee, Chang-Min;Jung, In-Duk;Jeong, Young-Il;Chun, Sung-Hak;Park, Hee-Ju;Choi, Il-Whan;Ahn, Soon-Cheol;Shin, Yong-Kyoo;Lee, Sang-Yull;Yeom, Seok-Ran;Kim, Jong-Suk;Park, Yeong-Min
    • Journal of Life Science
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    • v.17 no.8 s.88
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    • pp.1090-1099
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    • 2007
  • Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.

Anti-inflammatory Activity of Crinum asiaticum Linne var. Japonicum Extract and its Application as a Cosmeceutical Ingredient (문주란의 항염효과와 화장료적 특성)

  • Kim, Ki-Ho;Kim, Young-Heui;Kim, Ki-Soo;Park, Sun-Hee;Lee, Soo-Hee;Kim, Young-Jin;Kim, Young-Sil;Kim, Jong-Heon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.1 s.55
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    • pp.59-64
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    • 2006
  • Crinum asiaticum Linne var. japonicum has long been used as a rheumatic remedy, an anti-pyretic, an anti-ulcer treatment, and for the alleviation of local pain and fever in Korea and Malaysia. In order to investigate the possibility of Crinum asiaticum Linne var. japonicum extract as a cosmetic ingredient, we measured its anti-inflammatory effect by inhibition of iNOS (inducible nitric oxide synthase), and the release of PGE2, IL-6, and IL-8. HPLC experiment after extraction with 95% ethanol at pH 3.5 showed that Crinum asiaticum Linne var. japonicum was mainly composed of lycorine (up to 1%), a well-known immunosuppressant. The content of lycorine varied depending on the type of tissue analyzed and the extraction method. In anti-inflammatory assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)- activated mouse macrophage RAW 264.7 cells, the ethanolic extract of Crinum asiaticum showed inhibitory activity of NO production in dose-dependent manner ($IC_{50} = 83.5 {\mu}g/mL$). Additional study by RT-PCR demonstrated that the extract of Crinum asiaticum significantly suppressed the expression of the iNOS gene. Moreover, the extract of Crinum asiaticum did not show my cytotoxicity, but did show cell proliferation effect against LPS ($10{\sim}60%$ increase of tell viability). In an assay to determine inhibition of the $H_2O_2$-activated release of PGE2, IL-6, and IL-8 in human normal fibroblast cell lines, the release of PGE2 and IL-6 was almost completely inhibited above concentrations of 0.05% and 1%, respectively. Moreover, the release of IL-8 was completely inhibited over the entire range of concentrations (> 0.0025%). The result showed that the extract of Crinum asiaticum Linne var. japonicum has sufficient anti-inflammatory effect. There-fore, Crinum asiaticum Linne var. japonicum extract may be useful as an ingredient of cosmetic products.

Efficiency of microspore embryogenesis in Brassica rapa using different genotypes and culture conditions (배추 유전자원의 소포자 유래 배 발생 효율에 미치는 배양 조건 구명)

  • Seo, Mi-Suk;Sohn, Seong-Han;Park, Beom-Seok;Ko, Ho-Cheol;Jin, Mina
    • Journal of Plant Biotechnology
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    • v.41 no.3
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    • pp.116-122
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    • 2014
  • Total of fifty accessions of Brassica rapa with various morphological characteristics were used for production of double haploid plants though microspore culture in Brassica rapa. Among them, only 30 accessions induced embryos from microspores. The highest efficiency of embryo induction of 1.194 per bud was obtained from IT135449 of turnip type, while 3 accessions of sarson (winter oil) type did not generate embryo. The effect of heat shock periods for embryogenesis was also investigated with 4 accessions (IT135449; Turnip type, IT199710; Chinese cabbage type, IT212886; Pak choi type, IT218043; Summer oil type). The high productions of embryos were observed in IT135449, IT199710 and IT212886 when microspores were pre-cultured to $32^{\circ}C$ for 2 days. In IT218043, high embryogenesis was observed at the 3 days of heat shock treatment. The optimal condition of shoot regeneration for IT199710 was observed in MS medium supplemented with NAA $0.5mg{\cdot}L^{-1}$ and BAP $1mg{\cdot}L^{-1}$. In contrast, the IT135449 and IT212886 were observed high regeneration frequency in MS medium without plant growth regulators. All the plantlets regenerated from microspore-derived embryos have been successfully transplanted to soil, and bud self-pollinated seeds were produced from doubled haploid plants. This indicated that double-haploid genotype was likely generated naturally during embryogenesis process.

Effects of Agrimonia pilosa Ledeb. Water Extract on α-Glucosidase Inhibition and Glucose Uptake in C2C12 Skeletal Muscle Cells (짚신나물 열수 추출물의 α-Glucosidase 저해 효과 및 근육세포에서 포도당 이용에 미치는 영향)

  • Kim, Sang-Mi;Lee, Young Min;Kim, Mi-Ju;Nam, Song-Yee;Kim, Sung-Hee;Jang, Hwan-Hee
    • The Korean Journal of Food And Nutrition
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    • v.26 no.4
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    • pp.806-813
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    • 2013
  • Agrimonia pilosa Ledeb. is a medicinal plant with anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic activities. However, few studies of the anti-diabetic effect of A. pilosa on insulin resistance status have been performed. In the present study, the anti-diabetic effect of A. pilosa water extract (AP) was determined by investigating its ${\alpha}$-glucosidase inhibitory property, glucose utilization, and uptake, as well as insulin resistance mechanism of action in C2C12 skeletal muscle cells. Compared to positive control (acarbose), AP ($10mg/m{\ell}$) showed a similar ${\alpha}$-glucosidase inhibitory capacity. Glucose uptake was significantly increased by $1{\mu}m$ insulin treatment (p<0.05). However, palmitic acid (FFA, 1 mM) induced muscle insulin resistance and glucose uptake dysfunction. On the other hand, AP ($10{\mu}g/m{\ell}$) was capable of reversing the FFA-induced insulin resistance in C2C12 myotubes. Compared to control, AP ($100{\mu}g/m{\ell}$ without insulin) significantly increased the utilization of glucose (p<0.05) in C2Cl2 myotubes cultured in normal glucose (7 mM). AP treatment significantly increased the relative mRNA and protein expression levels of Akt. In particular, the effect of A. pilosa on the insulin signaling system is associated with the up-regulation of Akt genes and glucose uptake in C2Cl2 myotubes. These results suggest that A. pilosa is useful in the prevention of diabetes and the treatment of hyperglycemic disorders.

THE EFFECTS OF DRYING AGENTS AND BONDING AGENTS ON THE SHEAR BOND STRENGTH OF SEALANTS TO ENAMEL (치면건조제와 접착제의 사용에 따른 치면열구전색재의 전단결합강도에 관한 연구)

  • Lim, Hyun-Hwa;Jang, Ki-Taek;Kim, Chong-Chul;Hahn, Se-Hyun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.2
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    • pp.196-203
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    • 2003
  • The application of sealants is a highly technique-sensitive procedure, requiring an extremely dry field prior to placement. Moisture contamination of the etched enamel surface before sealant placement is cited as the main reason for sealant failure. The purpose of this study was to evaluate the effects of different methods of sealant application on the shear bond strength of sealants to enamel. In groups 1, 2, 3, 4 Teethmate(unfilled sealant) was used, while Ultraseal XTplus(filled sealant) was used in groups 5, 6, 7, 8. Groups 1 and 5(control) were acid etched for 15 seconds using 35% phosphoric acid, washed and then dried. In groups 2, 6 drying agents were applied, and in groups 3, 7 bonding agents were applied and light cured. In groups 4 and 8 both drying agent and bonding agent were applied. Then sealant was cured to the specimen using molds 3mm in diameter and 2mm in height. Thermocycling was performed and shear bond strength was finally measured. The following results were obtained : 1. Groups using filled sealant(groups 5, 6, 7, 8) showed higher shear bond strengths compared to groups using unfilled sealant(groups 1, 2, 3, 4). 2. Among groups using unfilled sealant(groups 1, 2, 3, 4), groups 2, 3, 4 showed significantly higher shear bond strength compared to group 1(p<0.05). There were no significant differences among groups 2, 3 and 4. 3. There were no significant differences(p>0.05) among groups using filled sealant(groups 5, 6, 7, 8). 4. When modes of fracture were examined, cohesive failure was observed in groups 2, 3 and 4.

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