• Title/Summary/Keyword: Co-inhibition

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Bee Venom Enhanced Cytotoxic Effect of Natural Killer Cells on Human Lung Cancer Through Inducing Extrinsic Apoptosis

  • Kim, Jung Hyun;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.31 no.1
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    • pp.111-119
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    • 2014
  • Objectives : I investigated whether Bee Venom can synergistically strengthen the cytotoxic effects of NK-92 cells, enhancing the inhibition of the growth of Lung Cancer Cells including A549 and NCI-H460 through induction of death receptor dependent extrinsic apoptosis and NO generation in the Nitro-oxide pathway. Methods : Bee Venom inhibited cell proliferation of A549 or NCI-H460 Human Lung Cancer Cells as well as NK-92 Cells. Moreover, when they were co-punctured with NK cells and concomitantly treated by 3 ${\mu}g/ml$ of Bee Venom, more influence was exerted on inhibition of proliferation of A549 or NCI-H460 Human Lung Cancer Cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2, DR3, DR6 in A549 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells and treatment of 3 ${\mu}g/ml$ of Bee Venom, compared to co-culture of NK-92 cells alone, whereas the expression of Fas, TNFR2, DR6 in NCI-H460 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells, representing no synergistic effects in the co-culture of NK-92 cell and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom. Coincidently, caspase-8, a expression of pro-apoptotic proteins in the extrinsic apoptosis pathway demonstrated same results as the above. Meanwhile, In NO generation, there is little change of NO generation in co-culture of NK-92 cells with A549 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, whereas increase of NO generation was shown in co-culture of NK-92 cells with NCI-H460 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, although synergistic effects by Bee Venom was not found. Conclusions : These present data provide that Bee Venom could be useful candidate compounds to enhance lung cancer growth inhibiting ability of NK-92 cells through DR expression and the related apoptosis.

Effect of Carbon Monoxide on the Monoamine Neurotansmitter and Synthetic Enzyme in Rat Brains (일산화탄소가 뇌내 신경전달물질 및 그 합성효소에 미치는 영향)

  • Yun, Jae-Soon
    • YAKHAK HOEJI
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    • v.34 no.6
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    • pp.384-394
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    • 1990
  • We studied the effect of carbon monoxide(CO)-induced bypoxia on monoamine neurotransmitter and their syntheitc enzyme in rat brain. When the rats were acute or chronic intoxicated at CO 5000 ppm for 30 minutes or 2000 ppm for 1 week each 3 hours, dopamine content increased significantly with decreasing of its turnover in striatum and norepinephrine content was diminished in hypothalamus. 5-hydroxytryptamine content was increased significantly and its turnover was decreased both in striatum and hypothalamus. Tyrosine hydroxylase activity was reduced in striatum. These results suggest that inhibition of TH activity in CO-induced hypoxia is owing to lack of oxygen supply threfore NE content is decreased. We suggest that increasing of dopamine and 5-hydroxytryptamine are due to reduction of its turnover.

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Development of a Natural Surfactant from Extracts of Saponaria officinalis L. (비누풀 잎 추출물로부터 천연 계면활성제 개발)

  • Jang, A Reum;Kim, Hyo Jeong;Kim, Kwang Soo;Park, Eun Kyung
    • KSBB Journal
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    • v.28 no.3
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    • pp.202-207
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    • 2013
  • In this study, saponin content of extract from modified preconditioning process was investigated in Saponaria officinalis L. for cosmetic natural surfactant. Saponin content in steamed leaves from S. officinalis L. was about three times more than that in dried leaves (tea saponin and quillaja saponin). And saponin extracts from steamed leaves was excellently shown in both forming force and forming stability. In emulsion activity, saponin extracts from steamed leaves had a similar level to quillaja saponin and tea saponin. Saponin extracts from steamed leaves in S. officinalis L. showed nontoxic effect below in $1,000{\mu}g/mL$ of concentration and dose-dependent inhibition of NO production. From the experiment, the extracts of S. officinalis L. showed good cosmetic agent.

Production of Monoclonal Antibody against the Principal Metabolite of Cocaine, Benzoylecgonine (코카인의 주대사물인 벤조일에코닌에 대한 단일클론 항체의 제작)

  • Nam, Kyung-Soo;Kim, Jae-Wha;Oh, Eun-Suk;Choi, Myung-Ja;Choi, In-Seong;Chung, Tai-Wha
    • YAKHAK HOEJI
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    • v.36 no.2
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    • pp.188-190
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    • 1992
  • Two clones of monconal antibodies(Co-1 and Co-2) against BSA-benzoylecgonine(BSABE) were produced. Both monoclonal antibodies showed high binding affinity to BSA-BE. Observing from ELISA inhibition assay, Co-1 reacted only weakly with soluble benzoylecgonine, while Co-2 showed considerable reactivity with soluble benzoylecgonine.

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Co-Stimulatory Receptors in Cancers and Their Implications for Cancer Immunotherapy

  • Seongju Jeong;Su-Hyung Park
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.3.1-3.20
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    • 2020
  • Immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-CTLA-4 therapeutic agents, are now approved by the Food and Drug Administration for treatment of various types of cancer. However, the therapeutic efficacy of ICIs varies among patients and cancer types. Moreover, most patients do not develop durable antitumor responses after ICI therapy due to an ephemeral reversal of T-cell dysfunction. As co-stimulatory receptors play key roles in regulating the effector functions of T cells, activating co-stimulatory pathways may improve checkpoint inhibition efficacy, and lead to durable antitumor responses. Here, we review recent advances in our understating of co-stimulatory receptors in cancers, providing the necessary groundwork for the rational design of cancer immunotherapy.

Glabridin Liposome Ameliorating UVB-Induced Erythema and Lethery Skin by Suppressing Inflammatory Cytokine Production

  • Zhang, Chijian;Lu, Yongjie;Ai, Yong;Xu, Xian;Zhu, Siyang;Zhang, Bing;Tang, Minghui;Zhang, Lanyue;He, Tinggang
    • Journal of Microbiology and Biotechnology
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    • v.31 no.4
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    • pp.630-636
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    • 2021
  • Glabridin, a compound of the flavonoid, has shown outstanding skin-whitening and anti-aging properties, but its water insolubility limits its wide application. Therefore, glabridin liposome (GL) has been developed to improve its poor bioavailability, while there are few studies to evaluate its amelioration of UVB- induced photoaging. This study is performed to investigate the amelioration of GL against UVB- induced cutaneous photoaging. The prepared GL has a spheroidal morphology with an average diameter of 200 nm. The GL shows lower cytotoxicity than glabridin, but it has a more effective role in inhibition of melanin. Moreover, the application of GL can effectively relieve UV radiation induced erythema and leathery skin, associated with the down-regulated expression of inflammatory cytokines (TNF-α, IL-6 and IL-10). Taken together, these results demonstrate that GL has potentials as topical therapeutic agents against UVB radiation induced skin damage through inhibiting inflammation.

Dishevelling Wnt and Hippo

  • Kim, Nam Hee;Lee, Yoonmi;Yook, Jong In
    • BMB Reports
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    • v.51 no.9
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    • pp.425-426
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    • 2018
  • As highly conserved signaling cascades of multicellular organisms, Wnt and Hippo pathways control a wide range of cellular activities, including cell adhesion, fate determination, cell cycle, motility, polarity, and metabolism. Dysregulation of those pathways are implicated in many human diseases, including cancer. Similarly to ${\beta}-catenin$ in the Wnt pathway, the YAP transcription co-activator is a major player in Hippo. Although the intracellular dynamics of YAP are well-known to largely depend on phosphorylation by LATS and AMPK kinases, the molecular effector of YAP cytosolic translocation remains unidentified. Recently, we reported that the Dishevelled (DVL), a key scaffolding protein between canonical and non-canonical Wnt pathway, is responsible for nuclear export of phosphorylated YAP. The DVL is also required for YAP intracellular trafficking induced by E-cadherin, ${\alpha}-catenin$, or metabolic stress. Note that the p53/LATS2 and LKB1/AMPK tumor suppressor axes, commonly inactivated in human cancer, govern the reciprocal inhibition between DVL and YAP. Conversely, loss of the tumor suppressor allows co-activation of YAP and Wnt independent of epithelial polarity or contact inhibition in human cancer. These observations provide novel mechanistic insight into (1) a tight molecular connection merging the Wnt and Hippo pathways, and (2) the importance of tumor suppressor contexts with respect to controlled proliferation and epithelial polarity regulated by cell adhesion.

Preparation and In Vivo Evaluation of Huperzine A-Loaded PLGA Microspheres

  • FU XU-DONG;GAO YONG-LIANG;PING QI-LENG;Ren Tang
    • Archives of Pharmacal Research
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    • v.28 no.9
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    • pp.1092-1096
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    • 2005
  • Huperzine A-loaded microspheres composed of poly(D,L-lactide-co-glycolide) were prepared by an O/w emulsion solvent evaporation method. The characterization of the microspheres such as drug loading, size, shape and release profile was described. The in vitro release in the initial 7 days was nearly linear with $10\%$ released per day. Thereafter drug release rate became slow gradually and about $90\%$ drug released at day 21. The in vitro release rate determined by dialysis bag method had a good correlation with the in vivo release rate. Huperzine A aqueous solution was intramuscularly injected (i.m.) at 0.4mg/kg and microspheres were intra­muscularly injected at 8.4 mg eq huperzine A/kg in rats. The maxium plasma concentration $(C_{max})$ after i.m. microspheres was only $32\%$ of that after i.m. solution. Drug in plasma could be detectd until day 14 and about $5\%$ of administered dose was residued at the injection site at day 14. The relative bioavailability of huperzine A microspheres over a period of 14 days was $94.7\%$. Inhibition of acyecholinesterase activity (AchE) in rat's cortex, hippocampus and striatum could sustain for about 14 days. In conclusion, huperzine A-loaded microspheres possessed a prolonged and complete drug release with significant inhibition of AchE for 2 weeks in rats.

Antiinflammatory Activity of Hyperin from Acanthopanax chiisanensis Roots

  • Lee, Sang-Hyun;Jung, Sang-Hoon;Lee, Yeon-Sil;Yamada, Masateru;Kim, Bak-Kwang;Ohuchi, Kazuo;Shin, Kuk-Hyun
    • Archives of Pharmacal Research
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    • v.27 no.6
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    • pp.628-632
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    • 2004
  • The chloroform and the ethyl acetate fractions from the roots of Acanthopanax chiisanensis exhibited a significant inhibition of prostaglandin E$_2$ (PGE$_2$)production in rat peritoneal macrophages stimulated by the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA). Hyperin was isolated as an active principle from the ethyl acetate fraction. It sup-pressed not only $PGE_2$ production but also nitric oxide (NO) production in vitro in a concentration dependent manner. their $IC_{50}$, being 24.3 and $32.9{\;}{\mu}M$, respectively. Hyperin also caused a significant inhibition of increase in acetic acid-induced vascular permeability in mice in vivo.

Improved Inhibition of Human Immunodeficiency Virus Type 1 Replication by Intracellular Co-overexpression of TAR and RRE Decoys in Tandem Array

  • Lee, Seong-Wook
    • Journal of Microbiology
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    • v.41 no.4
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    • pp.300-305
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    • 2003
  • Intracellular expression of RNA decoys, such as TAR or RRE decoy, has been previously shown to protect immune cells from human immunodeficiency virus type 1 (HIV-1) replication by inhibiting the binding of the HIV-1 regulatory protein to the authentic HIV RNA sequence. However, HIV-1 challenge experiments of primary human T cells, which express the RNA decoy, demonstrated that the cells were only transiently protected, and hence, more improved protocols for HIV-1 inhibition with the RNA decoys need to be developed. In this report, in order to develop a more effective RNA decoy, we analyzed and compared the ability of a series of RNA decoy derivatives in inhibiting HIV-1 replication in CEM cells. Using an improved tRNA cassette to express high levels of RNA decoy transcripts in cells, we found that co-expression of both TAR and RRE decoys, in the form of an aligned sequence in a single transcription cassette, much more potently blocked cells from HIV-1 than the expression of only one kind of RNA decoy. This observation will have an important implication for experiments involving optimization of clinical applications in RNA decoy-based gene therapy against HIV-1.