• Title/Summary/Keyword: $\beta-cell$ function

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S100A4 Gene is Crucial for Methionine-Choline-Deficient Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

  • Zhang, Yin-Hua;Ma, De-Qiang;Ding, De-Ping;Li, Juan;Chen, Lin-Li;Ao, Kang-Jian;Tian, You-You
    • Yonsei Medical Journal
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    • v.59 no.9
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    • pp.1064-1071
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    • 2018
  • Purpose: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. Materials and Methods: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. Results: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory ($TGF-{\alpha}$, $IL-1{\beta}$, IL-6) and profibrogenic cytokines ($TGF-{\beta}1$, COL1A1, ${\alpha}-SMA$) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. Conclusion: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

Hydrogen Permeation of SrCe0.95Gd0.05O3-α-Ce0.9Gd0.1O2-β Proton-Conducting Ceramic Membranes (프로톤 전도성 SrCe0.95Gd0.05O3-α-Ce0.9Gd0.1O2-β 복합체 멤브레인의 수소투과 특성)

  • Kim, Hwan-Soo;Yu, Ji-Haeng;Shin, Min-Jae
    • Journal of Hydrogen and New Energy
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    • v.22 no.2
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    • pp.161-167
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    • 2011
  • Proton conductors have attracted considerable attention for solid oxide fuel cell (SOFC), hydrogen pump, gas sensor, and membrane separators. Doped $SrCeO_3$ exhibits appreciable proton conductivity in hydrogen-containing atmosphere at high temperature. However commercial realization has been hampered due to the reactivity of $SrCeO_3$ with $CO_2$. The chemical stability and proton conductivity are dependent on dopant type. The purpose of this work is to investigate chemical stability of $SrCe_{0.95}Gd_{0.05}O_{3-\alpha}-Ce_{0.9}Gd_{0.1}O_{2-\beta}$ composites in $CO_2$ and $H_2$ gases. Thermogravimetric analysis (TGA) was performed in gaseous $CO_2$ and electrical conductivity of the composites were also measured between 500 and $900^{\circ}C$ in air and $H_2$ atmosphere. $SrCe_{0.95}Gd_{0.05}O_{3-\alpha}-Ce_{0.9}Gd_{0.1}O_{2-\beta}$ composite membranes showed good chemical stability of in $CO_2$ atmosphere and high conductivity at hydrogen condition. The hydrogen permeation of $SrCe_{0.95}Gd_{0.05}O_{3-\alpha}-Ce_{0.9}Gd_{0.1}O_{2-\beta}$ composite membranes was investigated as a function of volumetric content of $SrCe_{0.95}Gd_{0.05}O_{3-\alpha}$. The $SrCe_{0.95}Gd_{0.05}O_{3-\alpha}-Ce_{0.9}Gd_{0.1}O_{2-\beta}$(6:4) membrane with a thickness of 1.0 mm showed the highest hydrogen permeability with the flux reaching of 0.12 $ml/min{\cdot}cm^2$ at $800^{\circ}C$ in 100%$H_2/N_2$ as feed gas.

The Effect of Alkali- and Heat-Treated Titanium Surfaces on Differentiation of Osteoblast (티타니움 표면의 알칼리-열처리가 골모세포의 분화에 미치는 영향)

  • Kang, Choong Hee;Vang, Mong-Sook;Yang, Hong-so;Park, Sang-Won;Lim, Hyun-Pil
    • Journal of Dental Rehabilitation and Applied Science
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    • v.25 no.3
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    • pp.293-306
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    • 2009
  • In this study, the biological response of fetal rat calvarial cells on alkali- and heat-treated titanium was assessed. The results were as follows; Cell proliferation on alkali- and heat-treated surfaces showed significantly higher level than on the titanium-6aluminum-4vanadium (weight percentage: 6 % aluminum, 4 % vanadium, Ti-6Al-4V) surface (p<0.01). In ELISA analysis, concentration of $IL-1{\beta}$ and IL-6 were raised when the cells were grown to day 7. Pre-treatment with herbimycin, a known tyrosine kinase inhibitor, suppressed the production of IL-6 (p<0.01). In comparison to commercially pure titanium (grade II, cp-Ti) and Ti-6Al-4V alloy, alkali- and heat-treated titanium enhanced alkaline phosphatase activity (p<0.001). In RT-PCR analysis, alkaline phosphatase, bone sialoprotein, receptor activated nuclear factor ligand mRNA expression was increased alkali- and heat-treated titanium. Herbimycin and SB203580, p38 MAPK inhibitor, were repressed of $IL-1{\beta}-induced$ IL-6 mRNA expression. These results suggest that alkali- and heat-treated titanium stimulate osteoblasts differentiation and facilitate bone remodeling.

MiR-29a and MiR-140 Protect Chondrocytes against the Anti-Proliferation and Cell Matrix Signaling Changes by IL-1β

  • Li, Xianghui;Zhen, Zhilei;Tang, Guodong;Zheng, Chong;Yang, Guofu
    • Molecules and Cells
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    • v.39 no.2
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    • pp.103-110
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    • 2016
  • As a degenerative joint disease, osteoarthritis (OA) constitutes a major cause of disability that seriously affects the quality of life of a large population of people worldwide. However, effective treatment that can successfully reverse OA progression is lacking until now. The present study aimed to determine whether two small non-coding RNAs miR-29a and miR-140, which are significantly down-regulated in OA, can be applied together as potential therapeutic targets for OA treatment. MiRNA synergy score was used to screen the miRNA pairs that potentially synergistically regulate OA. An in vitro model of OA was established by treating murine chondrocytes with IL-$1{\beta}$. Transfection of miR-29a and miR-140 via plasmids was investigated on chondrocyte proliferation and expression of nine genes such as ADAMTS4, ADAMTS5, ACAN, COL2A1, COL10A1, MMP1, MMP3, MMP13 and TIMP metallopeptidase inhibitor 1 (TIMP1). Western blotting was used to determine the protein expression level of MMP13 and TIMP1, and ELISA was used to detect the content of type II collagen. Combined use of miR-29a and miR-140 successfully reversed the destructive effect of IL-$1{\beta}$ on chondrocyte proliferation, and notably affected the MMP13 and TIMP1 gene expression that regulates extracellular matrix. Although co-transfection of miR-29a and miR-140 did not show a synergistic effect on MMP13 protein expression and type II collagen release, but both of them can significantly suppress the protein abundance of MMP13 and restore the type II collagen release in IL-$1{\beta}$ treated chondrocytes. Compared with single miRNA transfection, cotransfection of both miRNAs exceedingly abrogated the suppressed the protein production of TIMP1 caused by IL-$1{\beta}$, thereby suggesting potent synergistic action. These results provided1novel insights into the important function of miRNAs' collaboration in OA pathological development. The reduced MMP13, and enhanced TIMP1 protein production and type II collagen release also implies that miR-29a and miR-140 combination treatment may be a possible treatment for OA.

Enhancing Effect of Zingiber Officinale Roscoe Extracts on Mouse Spleen and Macrophage Cells Activation (생강추출물 투여에 의한 마우스 비장세포 및 대식세포 활성 효과)

  • Ryu Hye Sook;Kim Jin;Park Sang Chul;Kim Hun Sook
    • Journal of Nutrition and Health
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    • v.37 no.9
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    • pp.780-785
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    • 2004
  • Recently many investigators have initiated searches for immunomodulating substances from natural food sources. Ginger (Zingiber officinale Roscoe) has been used as a raw material in many traditional preparations since the ancient time. This study was performed to investigate the immunomodulative effects of Zingiber officinale Roscoe in mice, using ex vivo experiments. In order to elucidate the immunomodulative effects of Ginger, water extracts of the plant were orally administrated into mice, and isolated splenocytes and macrophages were used as experimental model. In order to identify its ex vivo effect six to seven week old Balb/c mice were fed ad libitum on a chow diet and water extracts of ginger were orally administrated every other day for two weeks at two different concentrations (50 and 500 mg/kg b.w.). After preparing the single cell suspension, the proliferation of splenocytes was determined by MTT assay. The result of ex vivo study showed that the highest proliferation of splenocytes and macrophage activatation was seen in the mice orally administrated at the concentration of 500 mg/kg b. w. of ginger water extracts. In conclusion, this study suggests that ginger extracts nay enhance the immune function by regulating the splenocyte proliferation and cytokine prodution capacity by activated macrophages in mice.

Effects of Soo Jeom San on the Functions of Heart and Digestive Organs (수점산(手拈散)이 심장(心臟)과 소화기(消化器)에 미치는 영향(影響))

  • Lee, Key-Sang;Mun, Byeong-Sun;Kim, Sah-Gil
    • The Journal of Internal Korean Medicine
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    • v.11 no.2
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    • pp.148-169
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    • 1990
  • The Present experiment was designed to investigate the effects of Soo Jeom San on the function of heart and digestive organs. And thus it was analyzed the total acidity, recovery effect, and the other various enzyme activities such as ATPase, Creatine kinase, Aspartate transaminase, and Lactate dehydrogenase. The results were obtained as follows : 1. The Total acidity decreased after Soo JeomSan administration for 6 days, however the total acidity inoreased after the drug administration for 9 days, these phenomena demonstrate that Soo Jeom San acts as a dual factor. The mechanism of decreasing the total acidity was considered to the inhibition of ATPase activity used for HCI active transport from parietal cells. 2. Soo Jeom San recovered the islets of Langerhans which was disrupted by streptozotocin. The recovery mechanism was suggested that Soo Jeom San stimulates the ${\beta}-cell$ proliferation. 3. Soo Jeom San inhibited the enzyme activities such as Creatine kinase and Aspartate transaminase, however the drug activated Lactate dehydrogenase. According to the obtained results, Soo Jeom San may be used for curing gastric ulcer and myocardiac infarction.

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Effects of Thyroid function on Ovary, Uterus and Serum Concentrations of Steroid Hormone in Rats (흰쥐의 갑상선기능이 난소, 자궁 및 혈청 성 Steroid Hormone에 미치는 영향)

  • 서길웅;이규승;박창식
    • Korean Journal of Animal Reproduction
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    • v.9 no.2
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    • pp.113-123
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    • 1985
  • 1. The weights of ovary and uternus in the all treated groups were lighter than those in control group showing significantly differences from 4 weeks after treatment. The significant was not recognized between PTU and Thx. groups, and Thyro. and control groups. 2. In the histological changes of ovary, follicles were disa, pp.ared and alignment of membrana granulosa disnitergration in cell change were serious in Thx. and PTU groups and slight in Thyro. group. 3. In the histological changes of uterus, endometrial epithelium and lamina propria were atrophied from 3 weeks after treatment in Thx. group, from 4 weeks in PTU groups and from 5 weeks in Thyro. group. Muscular layers were atrophied with time elapse in the all treated groups. 4. The changes of the concentrations of serum progesterone at all observation times in Thx. and PTU groups were significantly decreased in comparison with those in control group. While those in Thyro. group were significantly increased in comparison with those in control group. 5. The concentration of serum estradiol-17$\beta$ at all observation times in all experimental groups were below 27.2pg/ml. Therefore, we did not detect any changes of the concentrations.

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DENTAL MANAGEMENT OF LEUKOCYTE DEFICIENCY IN A CHILD WITH SEVERE ORAL INVOLVEMENT (백혈구 접착 결핍 증후군 환아의 치과적 처치)

  • Kim, Hyun-Jin;Lee, Nan-Young;Lee, Sang-Ho
    • The Journal of Korea Assosiation for Disability and Oral Health
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    • v.3 no.1
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    • pp.26-30
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    • 2007
  • Leukocyte adhesion deficiency(LAD) is a rare autorecessive defect of phagocytic function resulting from a lack of leukocyte cell surface expression of ${\beta}_2$ integrin molecules(CD 18) that are essential for leukocyte adhesion to endothelial cells and chemotaxis. As a results, patients with LAD suffer from severe bacterial infections and impaired wound healing. A small number of patients with leukocyte adhesion deficiency-1 have a milder defect, with residual expression of CD18. These patients tend to survive beyond infancy; they manifest progressive severe periodontitis, alveolar bone loss, periodontal pocket formation, and partial or total premature loss of the primary and permanent dentitions. In this report, we report on a 7 year old girl with severe oral involvement. The most import focus should be to control infections to reduce the risk for future infection.

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In Vivo Expression of the PTB-deleted Odin Mutant Results in Hydrocephalus

  • Park, Sunjung;Lee, Haeryung;Park, Soochul
    • Molecules and Cells
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    • v.38 no.5
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    • pp.426-431
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    • 2015
  • Odin has been implicated in the downstream signaling pathway of receptor tyrosine kinases, such as the epidermal growth factor and Eph receptors. However, the physiologically relevant function of Odin needs to be further determined. In this study, we used Odin heterozygous mice to analyze the Odin expression pattern; the targeted allele contained a ${\beta}$-geo gene trap vector inserted into the 14t intron of the Odin gene. Interestingly, we found that Odin was exclusively expressed in ependymal cells along the brain ventricles. In particular, Odin was highly expressed in the subcommissural organ, a small ependymal glandular tissue. However, we did not observe any morphological abnormalities in the brain ventricles or ependymal cells of Odin null-mutant mice. We also generated BAC transgenic mice that expressed the PTB-deleted Odin (dPTB) after a floxed GFP-STOP cassette was excised by tissue-specific Cre expression. Strikingly, Odin-dPTB expression played a causative role in the development of the hydrocephalic phenotype, primarily in the midbrain. In addition, Odin-dPTB expression disrupted proper development of the subcommissural organ and interfered with ependymal cell maturation in the cerebral aqueduct. Taken together, our findings strongly suggest that Odin plays a role in the differentiation of ependymal cells during early postnatal brain development.

STRUCTURE, SYNTHESIS, AND BIOLOGICAL FUNCTION OF NATURAL PRODUCTS IN DEER ANTLER AND THEIR DERIVATIVES

  • Kim, So-Yeon;Jhon, Gil-Ja;Lee, Yoon-Jin;Cho, So-Hye;Han, So-Yeop
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.126-126
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    • 1998
  • Studies on natural products are of great interest, due to the limits in development of synthesized medicine and its side effects. Deer antler is the most popular cure-all type drug among Asian folk medicines. In this study, we newly isolated the biologically active components from chloroform extract and 70% ethanol extract of deer antler, and analyzed their structures. First, the structure of monoacetyldiglyceride in deer antler was identified. To investigate the structure-activity relationship of monoacetyldiglycerides, we synthesized diverse substituted glycerides from glycerol, and confirmed their structures by spectroscopic methods. Among seven structurally-interesting compounds tested in this study, compound 1,2,3,5, and 6 showed activity toward [Ca$\^$2+/]$\_$i/ increase in fura-2 loaded rat pancreatic acinar cells. Second, 70% ethanol extract of deer antler stimulated insulin release from rat pancreatic islets. We found the most effective fraction was CN-Es-8 in 70% ethanol extract, and it increased intracellular Ca$\^$2+/ concentration in pancreatic ${\beta}$-cell.

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