• Title/Summary/Keyword: Release mechanism

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S100A8 and S100A9 Secreted by Allergens in Monocytes Inhibit Spontaneous Apoptosis of Normal and Asthmatic Neutrophils via the Lyn/Akt/ERK Pathway (단구에서 분비되는 S100A8과 S100A9의 Lyn/Akt/ERK 경로를 통한 정상인과 천식질환 호중구의 세포고사 억제 효과)

  • Kim, In Sik;Lee, Ji-Sook
    • Korean Journal of Clinical Laboratory Science
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    • v.49 no.2
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    • pp.128-134
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    • 2017
  • Der p 1 and Der p 2 are essential allergens of house dust mite associated with the development of asthma. In the present study, we examined whether Der p 1 and Der p 2 induce a release of S100A8 and S100A9 in monocytes, which are involved in the regulatory mechanism of neutrophil apoptosis. We found that Der p 1 and Der p 2 significantly increased the secretion of S100A8 and S100A9 in normal monocytes. Moreover, S100A8 and S100A9 strongly suppressed the spontaneous apoptosis of normal and asthmatic neutrophils. The inhibitory effect of S100A9 was stronger than that of S100A8, and asthmatic neutrophils showed a higher inhibitory effect than normal neutrophils. S100A8 and S100A9 induced activation of Lyn, Akt, and ERK in a time-dependent manner. These findings elucidate the roles of Der p 1 and Der p 2 in the interaction between monocytes and neutrophils, as well as contributing to our knowledge of the pathogenesis of allergic diseases.

Breakthrough Cancer Pain (돌발성 암성 통증)

  • Seo, Min Seok;Shim, Jae Yong
    • Journal of Hospice and Palliative Care
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    • v.18 no.1
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    • pp.1-8
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    • 2015
  • Breakthrough cancer pain is a transient exacerbation of pain that occurs despite relatively well controlled background pain with around-the-clock analgesia. It is highly prevalent in patients with cancer pain, with an overall prevalence of 70~90%. Breakthrough cancer pain has several negative effects on quality of life, including a decrease in functional status and social relationship, and higher incidence of anxiety/depression. It also places a detrimental burden on their families, society, and the healthcare system. According to the pathogenic mechanism, breakthrough cancer pain is classified into two categories: idiopathic (or spontaneous) pain and incident pain. Episodes of breakthrough cancer pain have typical characteristics, including rapid onset (5~10 min), severe intensity, and short duration (30~60 min). However, there are some variations in timing and severity of pain among patients and episodes. Therefore, a thorough assessment of pain episodes is needed and management plan must be individualized to provide optimal treatment. Several immediate-release formulations such as oxycodone, morphine, and hydromorphone are widely used despite relatively slow onset of action. Recent studies have shown that transmucosal fentanyl preparations were effective for faster control of breakthrough pain. We hope to improve management of breakthrough cancer pain with more efficient analgesics in line with currently available evidence.

The effect of progressive tensional force on mRNA expression of osteoprotegerin and receptor activator of nuclear factor ${\kappa}B$ ligand in the human periodontal ligament cell (기계적 자극이 치주인대 세포의 osteoprotegerin과 receptor activator of nuclear factor ${\kappa}B$ ligand mRNA 발현에 미치는 영향)

  • Lee, Kie-Joo;Lee, Syng-Ill;Hwang, Chung-Ju;Ohk, Seung-Ho;Tian, Yu-Shin
    • The korean journal of orthodontics
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    • v.35 no.4 s.111
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    • pp.262-274
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    • 2005
  • Tooth movement is a result of mutual physiologic responses between the periodontal ligament and alveolar bone stimulated by mechanical strain. The PDL cell and osteoblast are known to have an influence on bone formation by controlling collagen synthesis and alkaline phosphatase activation. Moreover. recent studies have shown that the PDL cell and osteoblast release osteoprotegerin (OPG) and the receptor activator of nuclear factor ぉ ligand (RANKL) to control the level of osteoclast differentiation and activation which in turn influences bone resorption. In this study. progressively increased, continuous tensional force was applied to PDL cells. The objective was to find out which kind of biochemical reactions occur after tensional force application and to illuminate the alveolar bone resorption and apposition mechanism. Continuous and progressively increased tensile force was applied to PDL cells cultured on a petriperm dish with a flexible membrane The amount of $PGE_2$ and ALP synthesis were measured after 1, 3, 0 and 12 hours of force application. Secondly RT-PCR analysis was carried out for OPG and RANKL which control osteoclast differentiation and MMP-1 -8, -9, -13 aud TIMP-1 which regulate the resolution of collagen and resorption of the osteoid layer According to the results. we concluded that progressively increased, concluded force application to human PDL cells reduces $PGE_2$ synthesis, and increases OPG mRNA expression.

Role of Endothelium-derived Relaxing Factor in Cerebral Autoregulation in vivo (뇌혈류 자가조절에 대한 Endothelium-derived Relaxing Factor의 역할)

  • Hong Ki-Whan;Yu Sung-Suk;Rhim Byung-Yong
    • The Korean Journal of Pharmacology
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    • v.31 no.1 s.57
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    • pp.27-37
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    • 1995
  • In anesthetized rats, we examined the possibility that endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) released in response to cholinergic mechanism may contribute to the reflex autoregulation of cerebral blood flow. Suffusion with mock cerebrospinal fluid (CSF), containing acetylcholine (ACh, $10^{-9}{\sim}10^{-6}M$) evoked concentration-dependent vasodilatation of the resting pial artery (mean, $19.3{\pm}1.7{\mu}m$, n=36), which was significantly inhibited not only by $N{\omega}$-nitro-L-arginine (L-NNA, $10^{-5}M$) but also by methylene blue ($10^{-6}M$) and oxyhemoglobin ($10^{-6}M$). The muscarinic receptors in the endothelium of pial artery implicated in the release of EDRF were considered to be $M_1\;and\;M_3$ subtypes. When suffused with mock CSF containing L-arginine it caused a transient vasodilatation, which was strongly inhibited by LY 83583 ($10^{-5}M$), but not by L-NNA ($10^{-5}M$). Additionally, both ACh- and L-arginine-induced vasodilation were significantly inhibited by glibenclamide, a specific ATP-sensitive $K^+$ channel blocker. On the other hand, changes in pial arterial diameter were plotted as a function of changes in systemic arterial blood pressure. The slopes of regression lines for vasodilation and vasoconstriction were not affected by pretreatment with $10^{-5}M$ L-NNA, but significantly reduced by $3{\times}10^{-6}M$ glibenclamide. Thus it is suggested that the reflex vasodilation of rat pial arteries in response to a transient hypotension is not mediated by EDRF (NO).

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Spalling of Intermetallic Compound during the Reaction between Electroless Ni(P) and Lead-free Solders (무전해 Ni(P)과 무연솔더와의 반응 중 금속간화합물의 spalling 현상에 관한 연구)

  • Sohn Yoon-Chul;Yu Jin;Kang S. K.;Shih D. Y,;Lee Taek-Yeong
    • Journal of the Microelectronics and Packaging Society
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    • v.11 no.3 s.32
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    • pp.37-45
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    • 2004
  • Electroless Ni(P) has been widely used for under bump metallization (UBM) of flip chip and surface finish layer in microelectronic packaging because of its excellent solderability, corrosion resistance, uniformity, selective deposition without photo-lithography, and also good diffusion barrier. However, the brittle fracture at solder joints and the spatting of intermetallic compound (IMC) associated with electroless Ni(P) are critical issues for its successful applications. In the present study, the mechanism of IMC spatting and microstructure change of the Ni(P) film were investigated with varying P content in the Ni(P) film (4.6,9, and $13 wt.\%$P). A reaction between Sn penetrated through the channels among $Ni_3Sn_4$ IMCs and the P-rich layer ($Ni_3P$) of the Ni(P) film formed a $Ni_3SnP$ layer. Thickening of the $Ni_3SnP$ layer led to $Ni_3Sn_4$ spatting. After $Ni_3Sn_4$ spatting, the Ni(P) film directly contacted the molten solder and the $Ni_3P$ phase further transformed into a $Ni_2P$ phase. During the crystallization process, some cracks formed in the Ni(P) film to release tensile stress accumulated from volume shrinkage of the film.

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α-Asarone Modulates Activity of Matrix Metalloproteinase as well as Antioxidant Activity (α-Asarone이 항산화 활성 및 기질금속단백질 분해효소 활성 조절에 미치는 영향)

  • Park, Hye-Jung;Kim, Moon-Moo
    • Journal of Life Science
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    • v.25 no.9
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    • pp.1000-1006
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    • 2015
  • α-Asarone is the main component of Acorus gramineus, which is a widely used oriental traditional medicine. A. gramineus is known to have a variety of medicinal effects, such as anti-gastric ulcer, antiallergy and antioxidant activity. It is also known to inhibit the release of histamine. However, the mechanism of its action remains unclear in humans. In this study, the effects of α-asarone on matrix metalloproteinase (MMP) and its antioxidant effect in a cell-free system were examined in HT1080 cells. In an MTT assay, the effect of α-asarone on cell viability showed no cytotoxicity below 16 μM. In an antioxidant assay, α-asarone increased reducing power in a dose-dependent manner but not the scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. In addition, α-asarone exhibited the protective effect against DNA oxidation induced by hydroxyl radicals produced by the Fenton reaction. Furthermore, in a gelatin disk assay, α-asarone enhanced collagenase activity. It also increased the activities of MMP-2 and MMP-9 stimulated by phorbol 12-myristate 13-acetate (PMA) in a gelatin zymography. On the other hand, the activity of MMP-9 stimulated by phenazine methosulfate (PMS) but not that of MMP-2 was increased in the presence of α-asarone. These findings suggest that α-asarone could be a candidate for the prevention and treatment of pathological diseases related to oxidative stress and MMPs.

Study on the Anti-Inflammatory Activity and Mechanism of Medicinal Plants Used in the Treatment of Arthritis (관절염 치료에 사용되는 한약재들의 항 염증 활성과 기전에 관한 연구)

  • Kim, Yoo-Hyun;Park, Ho
    • Korean Journal of Clinical Laboratory Science
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    • v.48 no.3
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    • pp.176-182
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    • 2016
  • When inflammatory reaction is in progress, the macrophages release inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and product inflammatory mediators, including inducible nitric oxide synthase (iNOS) and prostaglandin E2 (PGE2). We conducted this study to evaluate the anti-inflammatory efficacy on each water extract of Acanthopanacis cortex, Achyranthes radix, and Eucommiae cortex, and to investigate whether they inhibit the expression of pro-inflammatory cytokine. Acanthopanacis cortex, Achyranthes radix, and Eucommiae cortex were extracted with water and freeze-dried. Acanthoside D, 20-hydroxyecdysone, and pinoresinol diglucoside as an index material were analyzed by high-performance liquid chromatography (HPLC) to ensure that the components of each extracts were extracted well. RAW 264.7 cell line, stimulated with lipopolysaccharide (LPS) to cause an inflammatory response, was treated with each water extract at various concentrations to determine the anti-inflammatory efficacy. Then, the anti-inflammatory efficacy was confirmed by a nitric oxide (NO) assay, and the mRNA expression levels of pro-inflammatory cytokines were measured by real time PCR. As a result, the indicator materials were detected from each extract, and Acanthopanacis cortex water extract (ACWE) and Achyranthes radix water extract (ARWE) were shown to have a high activity than Eucommiae cortex water extract (ECWE) in NO assay. In Korea, traditionally it prescribed a combination of medicinal herbs. This study confirmed the anti-inflammatory response of these medicinal plants in arthritis and its synergistic effect when used in combination with western medicine.

A Study on Antitumor Effect and Mechanism of Cortex ulmi pumilae Water Extract on HepG2 Hepatoma cell (유근피(楡根皮) 추출액(抽出液)이 HeoG2 간암세포(肝癌細胞)에 미치는 항암효과(抗癌效果) 및 기전(機轉)에 대(對)한 연구(硏究))

  • Choi, Su-Deock;Park, Young-Kweon;Kim, Gang-San;Kang, Byung-Ki;Han, Sang-Il
    • The Journal of Internal Korean Medicine
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    • v.21 no.2
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    • pp.259-266
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    • 2000
  • Objectives : The effects of aqueous extracts of Cortex ulmi pumilae (a traditional medicine for cancer treatment in oriental medicine) on the induction of apoptotic cell death were investigated in human liver origm hepatoma cell lines, HepG2. Methods : The death of HepG2 cells was markedly induced by the addition of extracts of Cortex ulmi pumilae in a dose-dependent manner. The apoptotic characteristic ladder pattern of DNA strand break was not observed in cell death of HepG2. In addition, it was not shown nucleus chromatin condensation and fragmentation under hoechst staining. However, by the using annexin V staining assay, externalizations of phosphatidylserine in HepG2 cell which were treated with Cortex ulmi pumilae extracts were detected in the early time (at 9 hr after extract treatment). Furthermore, LDH release was not detected in this early stage. Therefore, Cortex ulmi pumilae extracts-induced cell death of HepG2 cells is mediated by apoptotic death signal processes. Result : The activity of caspase 3-like proteases remained in a basal level in HepG2 cells which treated with the extract of Cordyceps sinensis. However, it was markedly increased in HepG2 cells which treated with two extracts of Cortex ulmi pumilae (C.U.P.-C, C.U.P.-K) which were differently extracted (respectively, 2.3 and 3.3 fold). On a while, the phosphotransferase activities of JNK1 was markedly induced in HepG2 cells which were treated with two extracts of Cortex ulmi pumilae. On the contrary, the activation of transcriptional activator, activating protein1(AP-1) and NF-kB were severely decreased by these two extracts of Cortex ulmi pumilae (C.U.P.-C, C.U.P.-K). In addition, antioxidants (GSH and NAC) and intracellular $Ca2^+$ level regulator (Bapta/AM and Thapsigargin) did not affect Cortex ulmi pumilae extracts-induced apoptotic death of HepG2 cells. Conclusions : In conclusion, our results suggest that two extracts of Cortex ulmi pumilae (C.U.P.-C, C.U.P.-K) induces the apoptotic death of human liver origin hepatoma HepG2 cells via activation of caspase 3-like proteases as well as JNK1, and inhibition of transcriptional activators, AP-1 and $NK-{\kappa}B$.

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Effects of Crataegii fructus on the Contractile Response of Rabbit Corpus Cavernosum (산사(山査)가 토끼 음경해면체의 수축에 미치는 영향)

  • Lee, Han Seok;Park, Sun Young
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.27 no.5
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    • pp.602-610
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    • 2013
  • This study was aimed to evaluate the cavernosal relaxation effect of Crataegii fructus(CF) in the contracted rabbit penile corpus cavernosum by agonists.In order to study the effect of CF on the vasoconstriction of rabbit penile corpus cavernosum, isolated rabbit penile corpus cavernosum tissues were used for the experiment using organ baths containing Krebs solution.To investigate the cavernosal relaxation of CF, CF extract at $0.01{\sim}3.0mg/m{\ell}$ was added after penile corpus cavernosum were contracted by norepinephrine(NE) $1{\mu}M$. To analyze the mechanism of CF's vasorelaxation, CF extract infused into contracted penile tissues by NE after each treatment of indomethacin(IM), $N{\omega}$-nitro-L-arginine(L-NNA), methylene blue(MB), tetraethylammonium chloride(TEA).To study the effect of CF on influx of extracellular calcium chloride($Ca^{2+}$) in penile tissues, in $Ca^{2+}$-free krebs solution, $Ca^{2+}$ 1 mM infused into contracted penile tissues by NE after pretreatment of CF. Cytotoxic activity of CF on human umbilical vein endothelial cell(HUVEC) was measured by MTT assay, and nitric oxide(NO) prodution was measured by Griess reagent. CF relaxed cavernosal strip with endothelium contracted by NE, but in the strips without endothelium, CF-induced relaxation was significantly inhibited. The pretreatment of L-NNA, MB, TEA decreased significantly on the cavernosal relaxation than not-treatment of them. But the pretreatment of IM had no significant effect on the cavernosal relaxation. In $Ca^{2+}$-free krebs solution, when $Ca^{2+}$ infused into contracted penile tissues by NE, pretreatment of CF inhibit contraction induced by adding $Ca^{2+}$.NO production wasn't increased by treatment of CF on HUVEC. This findings showed that CF is effective for the relaxation of rabbit penile corpus cavernosum, and we suggest that CF relax rabbit corpus cavernosal smooth muscle through multiple action mechanisms that include increasing the release of nitric oxide from corporal sinusoidal endothelium, inhibition of $Ca^{2+}$ mobilization into cytosol from the extracellular fluid, and maybe a hyperpolarizing action.

Anti-Inflammatory Effect of Licochalcone E, a Constituent of Licorice, on Lipopolysaccharide-Induced Inflammatory Responses in Murine Macrophages (Licochalcone E의 항염증 효과와 그 기전에 대한 연구)

  • Park, Geun-Mook;Jun, Jong-Gab;Kim, Jin-Kyung
    • Journal of Life Science
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    • v.21 no.5
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    • pp.656-663
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    • 2011
  • Licochalcone, a major phenolic constituent of the licorice species Glycyrrhiza inflata, a constituent of licorice, exhibits various biological properties, including chemopreventive-, antibacterial-, and anti-spasmodic activities. Recently, Licochalcone E (LicE) was isolated from the roots of Glycyrrhiza inflate, however its biological functions have not been fully examined. In the present study, we investigated the ability of LicE to regulate inflammation reactions in macrophages. Our in vitro experiments using murine macrophages, RAW264.7 cells, showed that LicE suppressed not only nitric oxide (NO) and prostaglandin $E_2$ generation, but also the expression of inducible NO synthase and cyclooxygenase-2 induced by lipopolysaccharide (LPS). Similarly, LicE inhibited the release of proinflammatory cytokines induced by LPS in RAW264.7 cells, including tumor necrosis factor-${\alpha}$ and interleukin-6. The underlying mechanism of LicE on anti-inflammatory action correlated with down-regulation of the nuclear factor-${\kappa}$B. Our data collectively indicate that LicE inhibited the production of several inflammatory mediators and might be used in the treatment of various inflammatory diseases.