• Title/Summary/Keyword: Selective Mechanism

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Combination of Doxorubicin with Gemcitabine-Incorporated G-Quadruplex Aptamer Showed Synergistic and Selective Anticancer Effect in Breast Cancer Cells

  • Joshi, Mili;Choi, Jong-Soo;Park, Jae-Won;Doh, Kyung-Oh
    • Journal of Microbiology and Biotechnology
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    • v.29 no.11
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    • pp.1799-1805
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    • 2019
  • Doxorubicin (DOX) is one of the most effective anticancer agents used for the treatment of multiple cancers; however, its use is limited by its short half-life and adverse drug reactions, especially cardiotoxicity. In this study, we found that the conjugate of DOX with APTA12 (Gemcitabine incorporated G-quadruplex aptamer) was significantly more cancer selective and cytotoxic than DOX. The conjugate had an affinity for nucleolin, with higher uptake and retention into the cancer cells than those of DOX. Further, it was localized to the nucleus, which is the target site of DOX. Owing to its mechanism of action, DOX has the ability to intercalate into the nucleotides thus making it a suitable drug to form a conjugate with cancer selective aptamers such as APTA12. The conjugation can lead to selectively accumulate in the cancer cells thus decreasing its potential nonspecific as well as cardiotoxic side effects. The aim of this study was to prepare a conjugate of DOX with APTA12 and assess the chemotherapeutic properties of the conjugate specific to cancer cells. The DOX-APTA12 conjugate was prepared by incubation and its cytotoxicity in MCF-10A (non-cancerous mammary cells) and MDA-MB-231 (breast cancer cells) was assessed. The results indicate that DOX-APTA12 conjugate is a potential option for chemotherapy especially for nucleolin expressing breast cancer with reduced doxorubicin associated side effects.

Evaluation of Cytotoxicity Effects of Chalcone Epoxide Analogues as a Selective COX-II Inhibitor in the Human Liver Carcinoma Cell Line

  • Makhdoumi, Pouran;Zarghi, Afshin;Daraei, Bahram;Karimi, Gholamreza
    • Journal of Pharmacopuncture
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    • v.20 no.3
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    • pp.207-212
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    • 2017
  • Objectives: Study of the mechanisms involved in cancer progression suggests that cyclooxygenase enzymes play an important role in the induction of inflammation, tumor formation, and metastasis of cancer cells. Thus, cyclooxygenase enzymes could be considered for cancer chemotherapy. Among these enzymes, cyclooxygenase 2 (COX-2) is associated with liver carcinogenesis. Various COX-2 inhibitors cause growth inhibition of human hepatocellular carcinoma cells, but many of them act in the COX-2 independent mechanism. Thus, the introduction of selective COX-2 inhibitors is necessary to achieve a clear result. The present study was aimed to determine the growth-inhibitory effects of new analogues of chalcone epoxide as selective COX-2 inhibitors on the human hepatocellular carcinoma (HepG2) cell line. Methods: Estimation of both cell growth and the amount of prostaglandin E2 (PGE2) production were used to study the effect of selective COX-2 inhibitors on the hepatocellular carcinoma cell. Cell growth determination has done by MTT assay in 24 h, 48 h and 72 h, and PGE2 production has estimated by using ELYSA kit in 48 h and 72 h. Results: The results showed growth inhibition of the HepG2 cell line in a concentration and time-dependent manner, as well as a reduction in the formation of PGE2 as a product of COX-2 activity. Among the compounds those analogues with methoxy and hydrogen group showed more inhibitory effect than others. Conclusion: The current in-vitro study indicates that the observed significant growth-inhibitory effect of chalcone-epoxide analogues on the HepG2 cell line may involve COX-dependent mechanisms and the PGE2 pathway parallel to the effect of celecoxib. It can be said that these analogues might be efficient compounds in chemotherapy of COX-2 dependent carcinoma specially preventing and treatment of hepatocellular carcinomas.

Roles of Serotonergic and Adrenergic Receptors in the Antinociception of Selective Cyclooxygenase-2 Inhibitor in the Rat Spinal Cord

  • Jeong, Hye-Jin;Lee, Seong-Heon;Cho, Soo-Young;Lee, Cha-Sup;Jeong, Cheol-Won;Yoon, Myung-Ha;Kim, Woong-Mo
    • The Korean Journal of Pain
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    • v.24 no.4
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    • pp.179-184
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    • 2011
  • Background: The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level. Methods: DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, ${\alpha}1$ adrenergic and ${\alpha}2$ adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test. Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level.

A Study on Selective Composite Patch for Light Weight and Quality Improvement of Battery Module (배터리 모듈의 경량화 및 품질 향상을 위한 선택적 복합재료 패치에 관한 연구)

  • Lee, Seung-Chan;Ha, Sung Kyu
    • Composites Research
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    • v.32 no.1
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    • pp.13-20
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    • 2019
  • In this study, in order to improve the quality issue and component characteristics of the battery module, which is one of the major parts of the electric vehicle. The structure is reinforced by using the composite material and the mechanism structure optimization of Hybrid concept which can overcome the disadvantages of single material was performed and the performance was compared. For this purpose, figure out the main design variables of composite materials according to Classical Laminated Plate Theory (CLPT) and the algorithm for predicting composite material properties have been studied. Based on the mechanical properties of the designed composite materials, finite element analysis (FEM) and the performance of the battery module was verified. Consequently, according to the verification result, Hybrid Battery Module reinforced with Selective Composite Patch can reduce the weight by 30% and reduce the product thickness by 32.5% compared with the existing Al battery module and proved the merit of Hybrid structure such as maintaining impact performance.

Current Guidelines for Non-Steroidal Anti-Inflammatory Drugs (비스테로이드 소염제의 최신 사용 지침)

  • Park, Min-Gyue;Yoo, Jae-Doo;Lee, Kyu-Ho
    • Journal of the Korean Orthopaedic Association
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    • v.55 no.1
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    • pp.9-28
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    • 2020
  • Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide for chronic pain, such as arthritis, and there are many different types depending on their composition and mechanism. After long-term use, various side effects can occur, such as gastrointestinal and cardiovascular complications. With a similar analgesic effect to that of traditional non-selective NSAIDs, cyclooxygenase-2-selective NSAIDs have been highly anticipated, because they could complement gastrointestinal tolerance. On the other hand, because of concerns about cardiovascular safety in 2004 and 2005, and the license withdrawals of rofecoxib and valdecoxib, the interest in the side effects of NSAIDs is increasing. Therefore, it is important to use the necessary drugs at a minimum, considering the side effects and interactions of each drug. This study examined the side effects and characteristics of each NSAID that may occur and reviewed the recent research and guidelines related to the use of non-selective NSAIDs and cyclooxygenase-2-selective NSAIDs.

A Comparison between the Decomposition of Bisphenol A and the Concentration of Hydrogen Peroxide Formed during Ozone/Catalyst Oxidation Process (오존/촉매 산화공정에서 비스페놀 A의 분해와 생성된 과산화수소의 농도 비교)

  • Choi, Jae Won;Lee, Hak Sung
    • Applied Chemistry for Engineering
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    • v.28 no.6
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    • pp.619-625
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    • 2017
  • In this study, the formation of hydroxyl radical and decomposition characteristics of bisphenol A (BPA) was investigated by quantifying hydrogen peroxide formed as a reaction by-product during the formation stage of hydroperoxyl radical. The direct oxidation reaction by ozone only decomposed BPA just like the Criegee mechanism under the condition where radical chain reactions did not occur. Non-selective oxidation reactions occurred under the conditions of pH 6.5 and 9.5 where radical chain reactions do occur, confirming indirectly the formation of hydroxyl radical. The decomposition efficiency of BPA by the added catalysts appeared in the order of $O_3$/PAC ${\geq}$ $O_3/H_2O_2$ > $O_3$/high pH > $O_3$ alone. 0.03~0.08 mM of hydrogen peroxide were continuously measured during the oxidation reactions of ozone/catalyst processes. In the case of $O_3$/high pH process, BPA was completely decomposed in 50 min of the oxidation reaction, but reaction intermediates formed by oxidation reaction were not oxidized sufficiently with 29% of the removal ratio for total organic carbon (TOC, selective oxidation reaction). In the case of $O_3/H_2O_2$ and $O_3$/PAC processes, BPA was completely decomposed in 40 min of the oxidation reaction, and reaction intermediates formed by the oxidation reaction were oxidized with 57% and 66% of removal ratios for TOC, respectively (non-selective oxidation reactions).

SACK TCP with Probing Device

  • Liang, Bing;Hong, Choong Seon
    • Proceedings of the Korea Information Processing Society Conference
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    • 2004.05a
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    • pp.1355-1358
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    • 2004
  • This paper describes a modification to the SACK (Selective Acknowledgement) Transmission Control Protocol's (TCP), called SACK TCP with Probing Device, SACK works in conjunction with Probing Device, for improving SACK TCP performance when more than half a window of data lost that is typical in handoff as well as unreliable media. It shows that by slightly modifying the congestion control mechanism of the SACK TCP, it can be made to better performance to multiple packets lost from one window of data.

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Depression, what should we be doing?

  • Ko, Kyung-Ja;Kim, Hyung-Min
    • CELLMED
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    • v.9 no.2
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    • pp.2.1-2.1
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    • 2019
  • Depression is common psychiatric diseases characterized by diverse physical and emotional symptoms including low mood, loss of interest in pleasurable activities, and feelings of worthlessness. Depression causes of death and disability. The first antidepressant was created by the idea that central serotonin mechanism. Selective serotonin reuptake inhibitor, fluoxetine is the first-line drug in the treatment of depressive disorder and their few side effects as opposed to tricyclic antidepressants. Not all people with depression respond adequately to standard treatments. Korean music playing/listening actions appear to be a reliable approach to developing recovery from depression.

Comparison of conotoxin gvia and cilnidipine on nicotinic receptor stimulation-induced catecholamine release in the rat Adrenal Galnd

  • Lim, Dong-Yoon
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.75.2-75.2
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    • 2003
  • The present study was designed to compare the effects of conotoxin GVIA, a selective blocker of N-type voltage-dependent calcium channels (VDCC) and cilnidipine, a blocker of both L- and N-type VDCC, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal gland, and also to establish the mechanism of action. 1. The inhibition of the CA secretory response evoked by acetylcholine (5.32 x 10$\^$-3/ ${\mu}$M) was stronger in cilnidipine-treated glands than in conotoxin GVIA-treated glands. (omitted)

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Wild Carrot Oil Extract is Selectively Cytotoxic to Human Acute Myeloid Leukemia Cells

  • Tawil, Mirna;Bekdash, Amira;Mroueh, Mohammad;Daher, Costantine F.;Abi-Habib, Ralph J.
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.761-767
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    • 2015
  • Background: In this study, we used Daucus carota oil extract (DCOE) to target acute myeloid leukemia (AML) cells. All the AML cell lines tested were sensitive to the extract while peripheral mononuclear cells were not. Analysis of mechanism of cell death showed an increase in cells positive for annexinV and for active caspases, indicating that DCOE induces apoptotic cell death in AML. Inhibition of the MAPK pathway decreased sensitivity of AML cells to DCOE, indicating that cytotoxicity may be dependent on its activity. In conclusion, DCOE induces selective apoptosis in AML cells, possibly through a MAPK-dependent mechanism.