• Title/Summary/Keyword: Modulation

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Effect of Astragalus Membranaceus Extract against Improvement of Myelosuppression and Quality of Life in 5-Fluorouracil Treated Mice (황기 추출물이 5-Fluorouracil을 투여한 생쥐의 골수억제 및 삶의 질에 미치는 영향)

  • Kwon, Chang-Hyun;Yoo, Hwa-Seung;Bang, Sun-Hwi;Lee, Young-Min;Lee, Yeon-Weol;Son, Chang-Gue;Cho, Chong-Kwan
    • The Journal of Internal Korean Medicine
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    • v.28 no.2
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    • pp.304-320
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    • 2007
  • Objective : To evaluate the effect of Astragalus Membranaceus Extrac (AME) on myelosuppression, activity and immune modulation in 5-fluorouracil (5-FU) treated mice. Method : We carried out complete blood count, histological analysis of bone marrow, and cell colony forming assay for hematopoietic progenitor to evaluate the effect of AME on myelosuppression and conducted swimming test, survival rate, nitric oxide (NO) assay, 51Cr release assay in natural killer cell, mRNA expression of $IL-1{\beta}$, IL-2, IL-4, IL-6, IL-10, $TNF-{\alpht}$, $IFN-{\gamma}$, $TGF-{\beta}$ and GM-CSF in spleen cells to evaluate the effect of AME on quality of life (QOL). Results : AME improved 5-FU induced myelosuppression and peripheral blood count was recovered effectively, had significant efficacy to protect against chemotherapy induced marrow-destruction and on hematopoiesis compared with the control group, improved increase survival rate and the swimming time, had a stimulatory effect on macrophage activation and NK cell activity, and up-regulated cytokine gene transcription (IL-2, IL-6, $IFN-{\gamma}$) in murine immunologic system. Conclusion : We can conclude that AM is an effective herbal agent for improvement of myelosuppression and QOL in 5-FU treated mice.

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Effects of Dohongsamul-Tang on the Gene Expression of Photothrombotic Ischemia Mouse Model (도홍사물탕(桃紅四物湯)이 광화학적 뇌경색 마우스의 유전자 발현에 미치는 영향)

  • Cho, Kwon-Il;Kim, Hye-Yoon;Ko, Seok-Jae;Lee, Seong-Geun;Shin, Sun-Ho;Moon, Byung-Soon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.3
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    • pp.645-661
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    • 2009
  • The water extract of Dohongsamul-Tang(DHSMT) has been traditionally used to stroke and brain injuries in Oriental Medicine. The present study was designed to investigate the effects of DHSMT on the gene expression profile of cerebral infarction by cDNA microarray in photothrombotic ischemia mouse model. Photothrombotic ischemia was induced in stereotactically held male BALB/c mice using rose bengal and cold light. MRI was performed 24 hours after inducing photothrombosis using 1.5 T MRI and 47 mm surface coil to obtain T2-weighted, and contrast-enhanced images. After MRI test, animal was sacrificed and the brain sections were stained for hematoxylin and eosin and immunohistochemistry. MRI and histological analysis revealed that lesion of thrombotic ischemia was well induced in the cortex with the evidence of biological courses of infarction. The target area of thrombotic infarction was 1 mm anterior to bregma and 3 mm lateral to midline with 2 mm in diameter, which were decreased by administration of DHSMT. To assess gene expression pattern of cerebral infarction, mRNA was isolated and reacted with microarray chip(Agilant's DNA Microarray 44K). Scatter and MA plot analysis were performed to clustering of each functional genes. M value [M=log2(R/G), A={log2(R ${\times}$ G)}/2] was between -0.5 and +0.5 with 40% difference. After pretreatment with DHSMT, the expression levels of mRNA of many genes involved in various signaling pathway such as apoptosis, cell cycle, cell proliferation, response to oxidative stress, immune response, angiogenesis, and inflammatory cytokine were markedly inhibited in photothrombotic ischemia lesion compared to the control group. These results suggest that DHSMT prevent ischemic death of brain on photothrombotic ischemia model of mice through modulation of gene expression at the transcriptional level.

Inhibitory Effects of Coptis japonica Alkaloids on the LPS-Induced Activation of BV2 Microglial Cells

  • Jeon, Se-Jin;Kwon, Kyung-Ja;Shin, Sun-Mi;Lee, Sung-Hoon;Rhee, So-Young;Han, Seol-Heui;Lee, Jong-Min;Kim, Han-Young;Cheong, Jae-Hoon;Ryu, Jong-Hoon;Min, Byung-Sun;Ko, Kwang-Ho;Shin, Chan-Young
    • Biomolecules & Therapeutics
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    • v.17 no.1
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    • pp.70-78
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    • 2009
  • Coptis japonica (C. japonica) is a perennial medicinal plant that has anti-inflammatory activity. C. japonica contains numerous biologically active alkaloids including berberine, palmatine, epi-berberine, and coptisine. The most well-known anti-inflammatory principal in C. japonica is berberine. For example, berberine has been implicated in the inhibition of iNOS induction by cytokines in microglial cells. However, the efficacies of other alkaloids components on microglial activation were not investigated yet. In this study, we investigated the effects of three alkaloids (palmatine, epi-berberine and coptisine) from C. japonica on lipopolysaccharide (LPS)-induced microglial activation. BV2 microglial cells were immunostimulated with LPS and then the production of several inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) were examined as well as the phosphorylation status of Erk1/2 mitogen activated protein kinase (MAPK). Palmatine and to a lesser extent epi-berberine and coptisine, significantly reduced the release of NO, which was mediated by the inhibition of LPS-stimulated mRNA and protein induction of inducible nitric oxide synthase (iNOS) from BV2 microglia. In addition to NO, palmatine inhibited MMP-9 enzymatic activity and mRNA induction by LPS. Palmatine also inhibited the increase in the LPS-induced MMP-9 promoter activity determined by MMP-9 promoter luciferase reporter assay. LPS stimulation increased Erk1/2 phosphorylation in BV2 cells and these alkaloids inhibited the LPS-induced phosphorylation of Erk1/2. The anti-inflammatory effect of palmatine in LPS-stimulated microglia may suggest the potential use of the alkaloids in the modulation of neuroinflammatory responses, which might be important in the pathophysiological events of several neurological diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and stroke.

Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake

  • Yang, Hong-Xu;Shang, Yue;Jin, Quan;Wu, Yan-Ling;Liu, Jian;Qiao, Chun-Ying;Zhan, Zi-Ying;Ye, Huan;Nan, Ji-Xing;Lian, Li-Hua
    • Biomolecules & Therapeutics
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    • v.28 no.4
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    • pp.320-327
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    • 2020
  • In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol-containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

Performance Analysis of Complex Phase-code for Phase Multiplexes Holographic Memory System (위상 다중화 홀로그래픽 메모리 시스템을 위한 CPC 위상코드의 성능 분석)

  • 조병철;김정진;김은수
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.28 no.1C
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    • pp.1-8
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    • 2003
  • In this paper, performance of the CPC(complex phase code) which is recently proposed as a practical phase encoding method for phase-code multiplexes holographic memory system is comparatively analyzed with those of the conventional phase codes such as PR(pure random code), RCE(random code with equality), WHM(Walsh Hadamard Matrix). In computer simulation, the size of an address bean is fixed at 32$\times$32 pixels and 0%-25% phase-error ratio in a pixel are intentionally added to the real phase values to consider the nonlinear phase-modulation characteristics of the practical spatial light modulator. From comparative analysis of crosstalks and signal-to-noise ratios for these phase codes by calculating auto-correlation and cross-correlation, it is found that the CPC have the lowest cross-correlation mean value of 0.021, the lowest standard deviation of 0.0113 and the highest signal-to-noise ratio(SNR) of 27.4 among the four types of phase code. In addition, from the calculation of the number of all possible address beams for these four types of phase code as the size of the address beam is fixed to 3232 pixels, the CPC is found to have 6.334$\times$10$^{49}$ address beams, which are relatively higher number than that of the conventional phase codes.

Transport parameters in a-Se:As films for digital X-ray conversion material using the moving-photocarrier-grating technique (moving-photocarrier-grating 기술을 이용한 디지털 X-선 변환물질 a-Se:As의 수송변수)

  • Park, Chang-Hee;Nam, Sang-Hee;Kim, Jae-Hyung
    • Journal of radiological science and technology
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    • v.28 no.4
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    • pp.267-272
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    • 2005
  • The effects of As addition in amorphous selenium (a-Se) films for digital X-ray conversion material have been studied using the moving photocarrier grating (MPG) technique. This method utilizes the moving interference pattern generated by the superposition of the two frequency shifted laser beams for the illumination of the sample. This moving intensity grating induces a short circuit current, jsc in a-Se:As film. The transport parameters of the sample are extracted from the grating-velocity dependent short circuit current induced in the sample along the modulation direction. The electron and hole mobility, and recombination lifetime of a-Se films with arsenic (As) additions have been obtained. We have found an increase in hole drift mobility and recombination lifetime, especially when 0.3% As is added into a-Se film, whereas electron mobility decreases with As addition due to the defect density. The transport properties for As doped a-Se films obtained by using MPG technique have been compared with X-ray sensitivity for a-Se:As device. The fabricated a-Se(0.3% As) device film exhibited the highest X-ray sensitivity out of 5 samples.

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Inhibitory Effects of a Herbal Composition (HemoHIM) on the Activation of Human Mast Cell Line (HMC-1) (생약복합조성물(HemoHIM)의 사람 비만세포주 활성 억제 효과)

  • Kim, Jong-Jin;Jo, Sung-Kee;Jung, U-Hee;Park, Hae-Ran;Yee, Sung-Tae
    • Journal of Life Science
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    • v.19 no.12
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    • pp.1808-1814
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    • 2009
  • In our previous study, a new herbal preparation (HemoHIM) was developed as a functional food for the radioprotection and immunomodulatory agents. In order elucidate the mechanism involved, we examined the effect of HemoHIM on the compound 48/80-induced histamine release, and on the phorbol 12-myristate 13-acetate (PMA)/calcium ionophore (A23187)-induced inflammatory cytokine secretion in HMC-1. The cell culture supernatants were harvested, and the cytokines (IL-4, IL-6, IL-8, TNF-$\alpha$, GM-CSF) in the supernatants were measured by enzyme-linked immunosorbent assay. The total RNA of the cells was extracted, and the cytokines or c-kit/tryptase/Fc$\varepsilon$RI's messenger RNA expressions were examined using reverse transcriptase polymerase chain reaction. Under low concentrations, HemoHIM inhibited histamine release in HMC-1 stimulated compound 48/80. Furthermore HemoHIM inhibited PMA/A23187-induced inflammatory cytokines' secreation or mRNA expression in a dose-dependent manner. But IL-8 secretion was not inhibited by low concentrayion of HemoHIM, respectively. The mRNA expression of c-kit and Fc$\varepsilon$RI were also inhibited in a dose-dependent manner. Tryptase mRNA expression was only inhibited by low concentration of HemoHIM. These results indicated that HemoHIM might be an useful agent for protection against allergy as well as immune modulation, especially since it is a relatively nontoxic natural product.

Rhythmic Control and Physiological Functional Significance of Melatonin Production in Circadian Rhythm (주기적 리듬 조절에 의한 멜라토닌 생산과 생리적 기능의 중요성)

  • Kim, Min Gyun;Park, Seul Ki;Ahn, Soon Cheol
    • Journal of Life Science
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    • v.23 no.8
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    • pp.1064-1072
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    • 2013
  • Circadian rhythm is controlled by hormonal oscillations governing the physiology of all living organisms. In mammals, the main function of the pineal gland is to transform the circadian rhythm generated in the hypothalamic suprachiasmatic nucleus into rhythmic signals of circulating melatonin characterized by a largely nocturnal increase that closely reflects the duration of night time. The pineal gland has lost direct photosensitivity, but responds to light via multi-synaptic pathways that include a subset of retinal ganglion cells. Rhythmic control is achieved through a tight coupling between environmental lighting and arylalkylamine-N-acetyltransferase (AANAT) expression, which is the rhythm-controlling enzyme in melatonin synthesis. Previous studies on the nocturnal expression of AANAT protein have described transcriptional, post-transcriptional, and post-translational regulatory mechanisms. Molecular mechanisms for dependent AANAT expression provide novel aspects for melatonin's circadian rhythmicity. Extensive animal research has linked pineal melatonin for the expression of seasonal rhythmicity in many mammalian species to the modulation of circadian rhythms and to sleep regulation. It has value in treating various circadian rhythm disorders, such as jet lag or shift-work sleep disorders. Melatonin, also, in a broad range of effects with a significant regulation influences many of the body's physiological functions. In addition, this hormone is known to influence reproductive, cardiovascular, and immunological regulation as well as psychiatric disorders.

Improvement of Neuronal Differentiation by PDE4 Inhibition in Human Bone Marrow-mesenchymal Stem Cells (인간 골수유래-중간엽 줄기세포(hBM-MSCs)에서 PDE4 억제조절을 통한 신경세포 분화 효율 개선)

  • Jeong, Da Hee;Joe, I-Seul;Cho, Goang-Won
    • Journal of Life Science
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    • v.26 no.12
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    • pp.1355-1359
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    • 2016
  • Human bone marrow mesenchymal stem cells (hBM-MSCs) can differentiate into various cell types including osteoblasts, adipocytes, chondrocytes, and myocytes. Previous studies, including our own, have shown that MSCs can also differentiate into neuron-like cells. However, their rate of neuronal differentiation is not sufficient for application to stem cell therapy, which requires well-defined cell types. For this purpose, we first examined the expression of neuronal lineage markers (GFAP, MAP-2, KCNH1, Nestin, NF-M, and Tuj-1) by real-time PCR, western blot, and immunocytochemical staining. The expressions of the astrocyte marker GFAP and neuronal markers NF-M and Tuj-1 increased in neuronal differentiated MSCs (dMSCs). To improve the neuronal differentiation efficiency, PDE4, an important signaling intermediator in the progression of neuronal differentiation, was modulated using well-known inhibitors such as rolipram or resveratrol and then differentiated into neuronal cells (Roli- or RSV-dMSCs). The expressions of NF-M, Tuj-1 were increased while that of GFAP decreased in Roli- and RSV-dMSCs, which were examined by real-time PCR, western blot, and immunocytochemical staining. From these experiments, we have found that the neuronal differentiation efficiency can be ameliorated by the modulation of PDE4 activity.

Conceptual Source Design and Dosimetric Feasibility Study for Intravascular Treatment: A Proposal for Intensity Modulated Brachytherapy (혈관내 방사선치료를 위한 이론적 선원 설계 및 선량적 관점에서의 적합성 연구: 출력변조를 이용한 근접치료에 대한 제안)

  • Kim Siyong;Han Eunyoung;Palta Jatinder R.;Ha Sung W.
    • Radiation Oncology Journal
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    • v.21 no.2
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    • pp.158-166
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    • 2003
  • Purpose: To propose a conceptual design of a novel source for intensity modulated brachytherapy. Materials and Methods: The source design incorporates both radioactive and shielding materials (stainless steel or tungsten), to provide an asymmetric dose intensity in the azimuthal direction. The intensity modulated intravascular brachytherapy was performed by combining a series of dwell positions and times, distributed along the azimuthal coordinates. Two simple designs for the beta-emitting sources, with similar physical dimensions to a $^{90}Sr/Y$ Novoste Beat-Cath source, were considered in the dosimetric feasibility study. In the first design, the radioactive and materials each occupy half of the cylinder and in the second, the radioactive material occupies only a quater of the cylinder. The radial and azimuthal dose distributions around each source were calculated using the MCNP Monte Carlo code. Results: The preliminary hypothetical simulation and optimization results demonstrated the 87$\%$ difference between the maximum and minimum doses to the lumen wall, due to off-centering of the radiation source, could be reduced to less than 7$\%$ by optimizing the azimuthal dwell positions and times of the partially shielded intravascular brachytherapy sources. Conclusion: The novel brachytherapy source design, and conceptual source delivery system, proposed in this study show promising dosimetric characteristics for the realization of intensity modulated brachytherapy in intravascular treatment. Further development of this concept will center on building a delivery system that can precisely control the angular motion of a radiation source in a small-diameter catheter.