• Title/Summary/Keyword: FSL-1

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Multiple Signaling Molecules are Involved in Expression of CCL2 and IL-$1{\beta}$ in Response to FSL-1, a Toll-Like Receptor 6 Agonist, in Macrophages

  • Won, Keunsoo;Kim, Sun-Mi;Lee, Sae-A;Rhim, Byung-Yong;Eo, Seong-Kug;Kim, Koanhoi
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.6
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    • pp.447-453
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    • 2012
  • TLR6 forms a heterodimer with TLR2 and TLR4. While proinflammatory roles of TLR2 and TLR4 are well documented, the role of TLR6 in inflammation is poorly understood. In order to understand mechanisms of action of TLR6 in inflammatory responses, we investigated the effects of FSL-1, the TLR6 ligand, on expression of chemokine CCL2 and cytokine IL-$1{\beta}$ and determined cellular factors involved in FSL-1-mediated expression of CCL2 and IL-$1{\beta}$ in mononuclear cells. Exposure of human monocytic leukemia THP-1 cells to FSL-1 resulted not only in enhanced secretion of CCL2 and IL-$1{\beta}$, but also profound induction of their gene transcripts. Expression of CCL2 was abrogated by treatment with OxPAPC, a TLR-2/4 inhibitor, while treatment with OxPAPC resulted in partially inhibited expression of IL-$1{\beta}$. Treatment with FSL-1 resulted in enhanced phosphorylation of Akt and mitogen-activated protein kinases and activation of protein kinase C. Treatment with pharmacological inhibitors, including SB202190, SP6001250, U0126, Akt inhibitor IV, LY294002, GF109203X, and RO318220 resulted in significantly attenuated FSL-1-mediated upregulation of CCL2 and IL-$1{\beta}$. Our results indicate that activation of TLR6 will trigger inflammatory responses by upregulating expression of CCL2 and IL-$1{\beta}$ via TLR-2/4, protein kinase C, PI3K-Akt, and mitogen-activated protein kinases.

Effect of Lactobacillus casei fermented Senna tora L. seeds and its active compound via muscarinic M3 signaling on the improvement of intestinal function in rats

  • Jang, Ji-Hun;Lee, Ki-Ho;Nho, Jong-Hyun;Lee, Hyun-Joo;Yang, Beo-Dul;Park, Ho;Cho, Hyun-Woo;An, Byeong-Kwan;Kim, Sun-Ra;Yong, Ju-Hyun;Park, Ro-Dong;Jung, Ho-Kyung
    • Journal of Applied Biological Chemistry
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    • v.63 no.4
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    • pp.365-373
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    • 2020
  • We previously reported the potential of Senna tora L. seeds fermented by Lactobacillus casei (FSL) as a laxative agent in a loperamide-induced constipation rat model. Here, we examine the mechanism of action of FSL and its bioactive compound, revealed herein, on loperamide-induced constipation Sprague Dawley rat model. We identified the compound aurantio-obtusin (AO) using HPLC quantitative analysis. Rats were randomly assigned to six experimental groups (eight rats each)-normal and constipated groups (loperamide, FSL [100, 300, 500 mg/kg], and AO [1 mg/kg]). The FSL and AO-treated group showed an increase in the frequency, amount, and water content of feces in the constipated rat. Moreover, FSL and AO increased the intestinal transit speed in the constipated rat. Histological analysis revealed that FSL and AO recovered the intestinal mucus, the number of goblet cells, as well as thickness of the mucosa layer and muscle. Furthermore, the protein levels of the muscarinic acetylcholine receptor M3, which is involved in intestine contraction, were recovered in the FSL and AO-treated group. Its downstream signaling pathway (p-protein kinase C) was recovered by FSL and AO treatment. In conclusion, fermentation of S. tora L. seeds increases AO, which improves intestinal function, indicating that FSL is effective for treating constipation.

A Study of Activities do Daily Living Performance on Arthritic Elderly Patients (노인의 퇴행성 슬관절염과 일상생활 수행력에 관한 연구)

  • Park Rae-Joon;Park Young-Han
    • The Journal of Korean Physical Therapy
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    • v.14 no.4
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    • pp.183-203
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    • 2002
  • To know the effect of index of social ability (ISA) and function of social life (FSL) with activities of daily living (ADL) and instrumental activities of daily living (IADL), we carried out a study on the elderly with osteoarthritis daily living in Daegu city for 4 months, from April to July 2002. The followings were observed: 1. The score of functional disability of knee, ADL and ISA were better at lower age (p < 0.01). 2. The younger they are, the better FSL they have. The lower age group has good FSL (p < 0.01). 3. Weight affects more to the under 49Kg group than 50-59Kg group and 60-69Kg group in functional disability of knee, while it doesn't make much difference for the other groups (p > 0.05) and other assessment index doesn't show any relationship with weight. 4. Regarding relat ionship with height , taller group has better knee functions: it's proved by post hock examination that the over 160cm group has much higher knee function than the other groups (p < 0.05). In case of ADL, the over 160cm group and under 149cm group were better than 150$\∼$159cm group. (p < 0.01) . 5. ISA was also different depending on height . It was proved that FSL was the better for the over 160cm group than for the others as a result of post hock examination (p < 0.05). 6. In regard of how many months have passed since the attack of functional disability of knee, knee joint function was better for the 12mon$\∼$36mon group than for the others and the score of ADL was lower for the 12mon$\∼$36mon group than for the others (p < 0.01). ISA was lower for the 12mon$\∼$36mon group and the under 6mon group than for the other groups (p < 0.01). FSL was lower for the 12mon$\∼$36mon group and the under 6mon group than the other groups. (p < 0.01). 7. Comparing left knee with right one, the problem with left knee has lower score of functional disability in all items (p < 0.01). 8. Considering friction noise, knee joint function was slightly better for non-friction noise-group, but it's not statistically significant though. ADL and ISA were better for non-friction noise-group (p < 0.01), while no statistical significance was found in FSL, 9. Knee joint function was better for the group who doesn't have limitation on range of knee flexion motion (p,0.05) but no other difference was found in other items from this group. 10. Limitation on range of knee flexion motion has no statistical difference in ADL and FSL. However, ISA was better for the non-limitation group (p < 0.05) . 11. Knee joint function score has high correlation with ISA (r=0.812, p < 0.01) and FSL (r=0.732, p < 0.01) , which shows the better knee joint function, the higher the score. 12. ISA and FSL were highly correlated: the better ISA, the better FSL (r=0.893, p < 0.01), while ADL has no correlation with either knee joint function or ISA or FSL.

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The Study of annealing condition and press method of glass for making glasses lens (안경렌즈 제작을 위한 유리의 열처리조건과 성형방법에 관한 연구)

  • Cha, Jung Won;Ha, Tae Wook
    • Journal of Korean Ophthalmic Optics Society
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    • v.6 no.1
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    • pp.133-137
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    • 2001
  • The method to make glass is tried first thing in domestic study for glasses lens. Tg of glass KzFSl was measured by DSC experiment and press method of glass of meniscus shape was studied for minimize the cost. Tg was increased $483^{\circ}C$ to $501^{\circ}C$ with increasing heating rate $2^{\circ}C/min$ to $20^{\circ}C/min$. It shows Arrhenius temperature dependence and the activation energy of Tg is ${\Delta}E$=409 kJ/mole(4.25eV) by using Ozawa method and Tg is near $480^{\circ}C$. The melt of KzFSl powder was poured to concave cast stainless and pressed convex cast stainless. The quenched glass was slow cooled with cooling rate $0.25^{\circ}C/min$ in temperature range $520{\sim}430^{\circ}C$. The glass was made without strain. It has meniscus shape and same size to commercial glasses lens.

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FSL-1, a Toll-like Receptor 2/6 Agonist, Induces Expression of Interleukin-$1{\alpha}$ in the Presence of 27-hydroxycholesterol

  • Heo, Weon;Kim, Sun-Mi;Eo, Seong-Kug;Rhim, Byung-Yong;Kim, Koanhoi
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.6
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    • pp.475-480
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    • 2014
  • We investigated the question of whether cholesterol catabolite can influence expression of inflammatory cytokines via Toll-like receptors (TLR) in monocytic cells. Treatment of THP-1 monocytic cells with 27-hydroxycholesterol (27OHChol) resulted in induction of gene transcription of TLR6 and elevated level of cell surface TLR6. Addition of FSL-1, a TLR6 agonist, to 27OHChol-treated cells resulted in transcription of the $IL-1{\alpha}$ gene and enhanced secretion of the corresponding gene product. However, cholesterol did not affect TLR6 expression, and addition of FSL-1 to cholesterol-treated cells did not induce expression of $IL-1{\alpha}$. Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and $IL-1{\alpha}$. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and $IL-1{\alpha}$ induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of $IL-1{\alpha}$. These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of $IL-1{\alpha}$ in monocytic cells via multiple signaling pathways.

7α-Hydroxycholesterol Elicits TLR6-Mediated Expression of IL-23 in Monocytic Cells

  • Seo, Hyun Chul;Kim, Sun-Mi;Eo, Seong-Kug;Rhim, Byung-Yong;Kim, Koanhoi
    • Biomolecules & Therapeutics
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    • v.23 no.1
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    • pp.84-89
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    • 2015
  • We investigated the question of whether 7-oxygenated cholesterol derivatives could affect inflammatory and/or immune responses in atherosclerosis by examining their effects on expression of IL-23 in monocytic cells. $7{\alpha}$-Hydroxycholesterol ($7{\alpha}OHChol$) induced transcription of the TLR6 gene and elevated the level of cell surface TLR6 protein in THP-1 monocytic cells. Addition of an agonist of TLR6, FSL-1, to TLR6-expressing cells by treatment with $7{\alpha}OHChol$ resulted in enhanced production of IL-23 and transcription of genes encoding the IL-23 subunit ${\alpha}$ (p19) and the IL-12 subunit ${\beta}$ (p40). However, treatment with 7-ketocholesterol (7K) and $7{\beta}$-hydroxycholesterol ($7{\beta}OHChol$) did not affect TLR6 expression, and addition of FSL-1 to cells treated with either 7K or $7{\beta}OHChol$ did not influence transcription of the genes. Pharmacological inhibition of ERK, Akt, or PI3K resulted in attenuated transcription of TLR6 induced by $7{\alpha}OHChol$ as well as secretion of IL-23 enhanced by $7{\alpha}OHChol$ plus FSL-1. Inhibition of p38 MAPK or JNK resulted in attenuated secretion of IL-23. These results indicate that a certain type of 7-oxygenated cholesterol like $7{\alpha}OHChol$ can elicit TLR6-mediated expression of IL-23 by monocytic cells via PI3K/Akt and MAPKs pathways.

Comparison of hemostatic efficacy and cytotoxicity of three ferric subsulfate- and chitosan-based styptics in different formulations using a rat tail bleeding model

  • Byun, Jae-Young;Lee, Soojung;Lee, Jeong Ik;Yoon, Hun-Young
    • Korean Journal of Veterinary Research
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    • v.58 no.3
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    • pp.119-124
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    • 2018
  • This study was conducted to compare the hemostatic efficacy of three ferric subsulfate- and chitosan-based styptics as a powder and a gel containing ferric subsulfate and chitosan (FSC-PO and FSC-G, respectively) and a soaked pad containing ferric subsulfate and lidocaine (FSL-SP) using a rat tail bleeding model. The cytotoxicity of the styptics against L-929 mouse fibroblasts was also evaluated using a cell counting kit-8 assay. Four groups of 10 rats each were assigned to the three different styptics and a non-treated control groups. Rat tail tips were transected, after which styptics were applied with pressure. The wounds were observed for hemostasis for 3 min, then irrigated with saline to check for recurrent hemorrhage. L-929 mouse fibroblasts were exposed to extracts of the styptics (100 mg/mL) and their dilutions (1:10, 1:100, and 1:1,000). FSC-PO and FSC-G more effectively controlled initial hemorrhage than FSL-SP (p = 0.033). Additionally, FSC-PO and FSC-G more effectively maintained hemostasis than the control group (p = 0.02 and p < 0.01, respectively). However, all styptics showed enhanced cytotoxicity against L-929 cells in a dose-dependent manner. Therefore, although FSC-PO and FSC-G would be recommended to control hemorrhage, the benefits of styptics must be balanced against the clinical significance of their cytotoxicity.

Comparison of Differences in Subcortical between Men and Women in their Seventies (70대의 성별에 따른 피질하부 차이 비교)

  • Ahn, Beyung-Ju;Park, Hye-Mi;Kim, Joo-Yeon;Lee, Jeong-hwan
    • Journal of the Korean Society of Radiology
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    • v.14 no.5
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    • pp.585-595
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    • 2020
  • Magnetic resonance imaging(MRI) has become an important technique for examining changes in human brain structure with neurological disorders. Brain development is a very complex process, and is affected by neurogenesiss and genetic programs. As age increases, structures of the brain change, which can contribute to the formation of brain diseases. Among the various factors, Gender is one of the greatest influential factors that affect the development of a healthy brain. The images were analyzed through various programs found in FSL such as SIENAX, FIRST, and Vertex analysis. Our results show that significant gender-related differences in subcortical areas were observed at the particular age group. The magnitude of these differences between gender and volume varied depending on the area investigated. In this study, we used more advanced 3T MRI for the structural analysis of subcortical structures between each gender. In addition, Vertex Analysis was used to visualize the volumetric differences in subcortical structures between each gender. This study is limited to groups in their 70s, therefore, further studies are needed for wider age groups.

Performance Evaluation of a Double Layer Biofilter System to Control Urban Road Runoff (I) - System Design - (이중층 토양 여과시설을 이용한 도로 강우 유출수 처리성능 평가 (I) - 시설 설계인자 결정을 중심으로 -)

  • Cho, Kang Woo;Kim, Tae Gyun;Lee, Byung Ha;Lee, Seul Bi;Song, Kyung Guen;Ahn, Kyu Hong
    • Journal of Korean Society of Water and Wastewater
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    • v.23 no.5
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    • pp.599-608
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    • 2009
  • This manuscript covers the results of field investigation and lab-scale experiments to design a double-layered biofilter system to control urban storm runoff. The biofilter system consisted of a coarse soil layer (CSL) for filtration and fine soil layer (FSL) for adsorption and biological degradation. The variations of flow rate and water quality of runoff from a local expressway were monitored for seven storm events. Laboratory column experiments were performed using seven kinds of soil and mulch to maximize pollutants removal. The site mean concentration (SMC) of storm runoff from the drainage area (runoff coefficient: 0.92) was measured to be 203 mg/L for SS, 307 mg/L for $TCOD_{Cr}$, 12.3 mg/L for TN, 7.3 mg/L for ${NH_4}^+-N$, and 0.79 mg/L for TP, respectively. This study employed a new design concept, to cover the maximum rainfall intensity with one month recurrence interval. Effective storms for last ten years (1998-2007) in seoul suggested the design rainfull intensity to be 8.8 mm/hr Single layer soil column showed the maximum removal rate of pollutants load when the uniformity coefficient of CSL was 1.58 and the silt/clay contents of FSL was virtually 7%. The removal efficiency during operation of double layer soil column was 98% for SS and turbidity, 75% for TCODCr, 56% for ${NH_4}^+-N$, 87% for TP, and 73-91% for heavy metals. The hydraulic conductivity of the soil column, 0.023 cm/sec, suggested that the surface area of the biofilter system should be about 1% of the drainage area to treat the rainfall intensity of one month recurrence interval.

Glucocorticoids Impair the 7α-Hydroxycholesterol-Enhanced Innate Immune Response

  • Yonghae Son;Bo-Young Kim;Miran Kim;Jaesung Kim;Ryuk Jun Kwon;Koanhoi Kim
    • IMMUNE NETWORK
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    • v.23 no.5
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    • pp.40.1-40.14
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    • 2023
  • Glucocorticoids suppress the vascular inflammation that occurs under hypercholesterolemia, as demonstrated in an animal model fed a high-cholesterol diet. However, the molecular mechanisms underlying these beneficial effects remain poorly understood. Because cholesterol is oxidized to form cholesterol oxides (oxysterols) that are capable of inducing inflammation, we investigated whether glucocorticoids affect the immune responses evoked by 7α-hydroxycholesterol (7αOHChol). The treatment of human THP-1 monocytic cells with dexamethasone (Dex) and prednisolone (Pdn) downregulated the expression of pattern recognition receptors (PRRs), such as TLR6 and CD14, and diminished 7αOHChol-enhanced response to FSL-1, a TLR2/6 ligand, and lipopolysaccharide, which interacts with CD14 to initiate immune responses, as determined by the reduced secretion of IL-23 and CCL2, respectively. Glucocorticoids weakened the 7αOHChol-induced production of CCL2 and CCR5 ligands, which was accompanied by decreased migration of monocytic cells and CCR5-expressing Jurkat T cells. Treatment with Dex or Pdn also reduced the phosphorylation of the Akt-1 Src, ERK1/2, and p65 subunits. These results indicate that both Dex and Pdn impair the expression of PRRs and their downstream products, chemokine production, and phosphorylation of signaling molecules. Collectively, glucocorticoids suppress the innate immune response and activation of monocytic cells to an inflammatory phenotype enhanced or induced by 7αOHChol, which may contribute to the anti-inflammatory effects in hypercholesterolemic conditions.

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