• Title/Summary/Keyword: rAD

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Post-Transcriptional Control of Tropoelastin in Aortic Smooth Muscle Cells Affects Aortic Dissection Onset

  • Qi, You-Fei;Shu, Chang;Xiao, Zhan-Xiang;Luo, Ming-Yao;Fang, Kun;Guo, Yuan-Yuan;Zhang, Wen-Bo;Yue, Jie
    • Molecules and Cells
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    • v.41 no.3
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    • pp.198-206
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    • 2018
  • Aortic dissection (AD) is a catastrophic disease with high mortality and morbidity, characterized with fragmentation of elastin and loss of smooth muscle cells. Although AD has been largely attributable to polymorphisms defect in the elastin-coding gene, tropoelastin (TE), other undermined factors also appear to play roles in AD onset. Here, we investigated the effects of post-transcriptional control of TE by microRNAs (miRNAs) on elastin levels in aortic smooth muscle cells (ASMC). We found that miR-144-3p is a miRNA that targets TE mRNA in both human and mouse. Bioinformatics analyses and dual luciferase reporter assay showed that miR-144-3p inhibited protein translation of TE, through binding to the 3'-UTR of the TE mRNA. Interestingly, higher miR-144-3p levels and lower TE were detected in the ASMC obtained from AD patients, compared to those from non-AD controls. In a mouse model for human AD, infusion of adeno-associated viruses (serotype 6) carrying antisense for miR-144-3p (asmiR-144-3p) under CAG promoter significantly reduced the incidence and severity of AD, seemingly through enhancement of TE levels in ASMC. Thus, our data suggest an essential role of miR-144-3p on the pathogenesis of AD.

Gene Expression of Enzymes Related to Glutathione Metabolism in Anticancer Drug-resistant L1210 Sublines (항암제 내성 L1210세포의 Glutathione 대사 관련효소 유전자의 발현 양상)

  • Kim, Seong-Yong;Kim, Jae-Ryong;Kim, Jung-Hye
    • Journal of Yeungnam Medical Science
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    • v.12 no.1
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    • pp.32-47
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    • 1995
  • Glutathione(GSH) has a very important role in detoxification of cells and is closely related to antitumor drug-resistance of cancer cells. In order to evaluate the importance of glutathione metabolism in the drug-resistant cancer cells, the concentration of celluar GSH and activities of ${\gamma}$-glutamylcysteine synthetase(GCS), ${\gamma}$-glutamyl transpeptidase (GGT) and glutathione S-transferases(GST) in the adriamycin, vincristine, or cisplatin resistant L1210 (L1210AdR, L1210VcR, or L1210Cis) sublines were measured. Expression and amplification of GCS, GGT, and GST-${\pi}$ genes were also observed in the parent Ll210 and the drug-resistant Ll210 sublines. The concentration of GSH was increased 5.34 fold in L1210Cis, 2.83 fold in L1210VcR, and 1.78 fold in L1210AdR, compared to L1210. The activities of GCS and GGT were increased in drug-resistant L1210 sublines. The GST activity was increased in L1210VcR and L1210Cis but decreased in L1210AdR compared to Ll210. Expression of GCS, GGT, and GST-${\pi}$ genes were increased in the resistant L1210 sublines compare to the parent L1210 in northern blot analyses. Overexpression of GCS, GGT, and GST-${\pi}$ were observed in the resistant sublines, and the increases of the concentration of glutathione and the activities of GCS and GGT in the resistant sublines may be involved in a part of the drug-resistance in the resistant sublines.

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Membrane Protein Alterations Associated with Anticancer Drug Resistance in Mouse Lymphoblastic Leukemia L1210 Cells (항암제에 내성인 생쥐의 백혈병세포 L1210의 세포막 단백질의 변환)

  • Kim, Seong-Yong;Son, Sung-Kweon;Kim, Jae-Ryong;Kim, Jung-Hye
    • Journal of Yeungnam Medical Science
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    • v.10 no.2
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    • pp.432-444
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    • 1993
  • Multidrug resistance(MDR) phenotype is frequently observed in animal and human cancer cell lines selected for in vitro resistance to a single chemotherapeutic agent. It is characterized by the diminished drug accumulation and is related to the drug efflux mechanism in resistant cells. In the present study, adriamycin resistant cells(L1210-$AdR_6$ : $10^{-6}M$ adriamycin, $-AdR_5$ : $10^{-5}M$) and vincristine resistant cells (L1210-$VcR_7$ : $10^{-7}M$ vincristine, $-VcR_6$ : $10^{-6}M$) were produced from mouse lymphoblastic leukemia cell line L1210. Growth profiles of survived cells were observed for 5 days with MTT(thiazolyl blue) assay and resistance was compared with $IC_{50}$(drug concentration of 50% survival reduction in absorbance). Resistant cells proliferated more slowly than sensitive cell. Doubling times were 29.7hr in L1210, 68.7hr in L1210-$AdR_5$ and 58.2hr in $-VcR_6$. MDRs expressed as resistance factor were as follows, L1210-$AdR_5$ was 76.4 times for vincristine, L1210-$VcR_6$ was 96.4 times for adriamycin. The cell membrane proteins with three different M.W. were recognized to be related resistance, 220, 158, and 88 kd in L1210-$AdR_5$, 158, 140 and 88 kd in L1210-$VcR_6$ by SDS-PAG electrophoresis. Cell surface membrane proteins were identified by radio-iodination and autoradiogram, their molecular weights were 158, 72.8, and 42.4 Kd in L1210-$VcR_6$.

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Apoptotic Effect of Ethanol Extracts of Bojungbangamtang and Acidic Polysaccharide of Korea Red Ginseng in a MCF7/adR Multidrug-resistance Breast Cancer Cells (항암제 내성 유방암 MCF7/adR 세포주에 대한 보정방암탕과 홍삼산성다당체의 세포고사 유도효과)

  • Ahn, Gyu-In;Park, Cheol-Hwan;Lee, Eun-Ok;Lee, Hyo-Jung;Lee, Jae-Ho;Kim, Kwan-Hyun;Rhee, Yun-Hee;Jang, Yu-Sung;Kim, Sang-Tae;Kim, Sung-Hoon
    • YAKHAK HOEJI
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    • v.50 no.4
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    • pp.272-277
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    • 2006
  • This study was undertaken to determine whether the 9 herbal complex induces apoptosis in human breast cancer MCF-7 cells and adriamycin-resistant MCF7/adR cells. Ethanol extracts of Bojungbangamtang (BBTE) and acidic polysaccharide of Red Ginseng (GIN) induced cell death in both MCF-7 and MCF7/adR cells. Ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng also induced $G_2/M$ cell cycle arrest and increased TUNEL positive cells in MCF7/adR cells. In addition, flow cytometric analysis revealed the decreased expression of P-glycoprotein (P-gp) in ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng treated MCF7/adR cells. Similarly, decreased protein levels of P-glycoprotein and multidrug resistance associated proteins-1 were also determined by immunocytometry in ethanol extracts of Bojungbangamtang treated MCF7/adR cells. Taken together these data indicate that ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng inhibit the function of ABC transporters such as multi drug resistance associated proteins (MRPs) and P-glycoprotein as well as induce apoptosis in MCF7/adR cells. Thus, these data suggest that ethanol extracts of Bojungbangamtang and polysaccharide of Red Ginseng can be candidates for the treatment of multidrug-resistant MCF7/adR cells.

A Probiotic Preparation Alleviates Atopic Dermatitis-Like Skin Lesions in Murine Models

  • Kim, Min-Soo;Kim, Jin-Eung;Yoon, Yeo-Sang;Seo, Jae-Gu;Chung, Myung-Jun;Yum, Do-Young
    • Toxicological Research
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    • v.32 no.2
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    • pp.149-158
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    • 2016
  • Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex etiology that encompasses immunologic responses. AD is frequently associated with elevated immunoglobulin (Ig) E levels, and common environmental factors contribute to its pathogenesis. Several recent studies have documented the role of specific lactic acid bacteria in the treatment and prevention of AD in humans and mice. In this study, the efficacy of Duolac ATP, a probiotic preparation, was determined in a mouse model with AD-like skin lesions. Alterations in the cytokine levels and histological staining suggested the alleviation of AD. The in vivo test showed that T helper (Th)2 cytokines, IgE, interleukin (IL)-4, and IL-5, were significantly downregulated, whereas Th1 cytokines, IL-12p40 and interferon (IFN)-${\gamma}$, were upregulated in all groups of mice treated with Duolac ATP compared to that observed in the group of mice treated with 1-chloro-2,4-dinitrobenzene (DNCB) alone. Moreover, the scratch score decreased in all mice treated with Duolac ATP. Staining of the dorsal area of the mice in each group with hematoxylin and eosin and toluidine blue further confirmed the alleviation of AD in mice orally treated with Duolac ATP. These results suggest that Duolac ATP inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the Th2 cell response and increasing the Th1 cell response. Thus, Duolac ATP is beneficial and effective for the treatment of AD-like skin lesions.

A Study on Laryngeal Behavior of Persons Who Stutter with Fiber-Optic Nasolaryngoscope (후두 내시경(Fiber-Optic Nasolaryngoscope)을 이용한 말더듬인의 후두양상에 관한 연구)

  • Jung, Hun;Ahn, Jong-Bok;Choi, Byung-Heun;Kwon, Do-Ha
    • Speech Sciences
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    • v.15 no.3
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    • pp.159-173
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    • 2008
  • The purpose of this study was to use fiber-optic nasolaryngoscope to find out differences in laryngeal behavior between persons who stutter(PS) and those who do not stutter(NS) upon their utterance. To meet the goal above, this study took 5 NS and 5 PS respectively as a part of sampling, so that they were all asked to join an experiment hereof. As a result, this study came to the following findings: First, there was not any significant difference in laryngeal behavior of uttering spoken languages between stuttering group and control. Second, there were some differences in laryngeal behavior of repetition and prolongation, which were a sort of disfluency revealed in the utterance of nonfluent spoken languages between stuttering group and control. Third, as reported by prior studies, it was found that there were differences in laryngeal abehavior of stutterer group's nonfluent spoken languages depending upon stuttering types. In this study, a variety of laryngeal behavior unreported in prior studies could be found. In addition, it was notable that stutterers showed different laryngeal behavior depending on their personal stuttering types. On block condition, Subject 1 showed laryngeal behavior of fAB, INT and fAD; Subject 2 showed laryngeal behavior of fAB, fAD and rAD; Subject 3 showed laryngeal behavior of fAD and rAD; Subject 4 showed only laryngeal behavior of fAD; and Subejct 5 showed laryngeal behavior of fAB, fAD and rAD. Summing up, these findings imply that when stutterers utter nonfluent words, they may reveal a variety of laryngeal behavior depending on their personal stuttering types. Moreover, it is found that there are more or less differences in the utterance of nonfluent spoken languages between NS and stuttering ones. In particular, it is interesting that one common trait of nonfluent spoken languages uttered by PS is evidently excessive laryngeal stress, no matter which type of stuttering they reveal.

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Expression of Multidrug Resistance-associated Protein (MRP), c-myc and c-fos in L1210 Cells (L1210 암세포에서 Multidrug Resistance-associated Protein (MRP), c-myc 및 c-fos 유전자의 발현양상)

  • Kim, Seong-Yong
    • Journal of Yeungnam Medical Science
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    • v.14 no.1
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    • pp.67-76
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    • 1997
  • The occurrence of multidrug resistance (MDR) is one of the main obstacles in the successful chemotherapeutic treatment of cancer. In this study The gene expressions of multidrug resistance-associated protein (MRP), c-myc and c-fos were investigated in L1210 cells. Adriamycin- or vincristine-resistant L1210 cells, L1210AdR or L1210VcR, respectively, has been identified to overexpression of mdr1 gene. The expression leve of MRP gene in L1210AdR and L1210Cis was more decreased than that in L1210 cells. The c-myc and c-fos genes were expressed both in L1210 and resistant sublines. In L1210AdR, the expressions level of c-myc and c-fos genes were decreased than in L1210. However, in L1210VcR and L1210Cis, c-myc and c-fosgene expressionwere rather increased than L1210. These results suggested that MRP does not contribute in resistance of drug-resistant L1210 cells and there is no relations between MRP and mdr1 gene expression. The expression of c-myc and c-fos gene may be changed during transformation of L1210 to drug-resistant sublines.

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Associations between Brain Perfusion and Sleep Disturbance in Patients with Alzheimer's Disease

  • Im, Jooyeon J.;Jeong, Hyeonseok S.;Park, Jong-Sik;Na, Seung-Hee;Chung, Yong-An;Yang, YoungSoon;Song, In-Uk
    • Dementia and Neurocognitive Disorders
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    • v.16 no.3
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    • pp.72-77
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    • 2017
  • Background and Purpose Although sleep disturbances are common and considered a major burden for patients with Alzheimer's disease (AD), the fundamental mechanisms underlying the development and maintenance of sleep disturbance in AD patients have yet to be elucidated. The aim of this study was to examine the correlation between regional cerebral blood flow (rCBF) and sleep disturbance in AD patients using technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT). Methods A total of 140 AD patients were included in this cross-sectional study. Seventy patients were assigned to the AD with sleep loss (SL) group and the rest were assigned to the AD without SL group. SL was measured using the sleep subscale of the Neuropsychiatric Inventory. A whole-brain voxel-wise analysis of brain SPECT data was conducted to compare the rCBF between the two groups. Results The two groups did not differ in demographic characteristics, severity of dementia, general cognitive function, and neuropsychiatric symptoms, with the exception of sleep disturbances. The SPECT imaging analysis displayed decreased perfusion in the bilateral inferior frontal gyrus, bilateral temporal pole, and right precentral gyrus in the AD patients with SL group compared with the AD patients without SL group. It also revealed increased perfusion in the right precuneus, right occipital pole, and left middle occipital gyrus in the AD with SL group compared with the AD without SL group. Conclusions The AD patients who experienced sleep disturbance had notably decreased perfusion in the frontal and temporal lobes and increased rCBF in the parietal and occipital regions. The findings of this study suggest that functional alterations in these brain areas may be the underlying neural correlates of sleep disturbance in AD patients.

Effect of fermented red ginseng on gut microbiota dysbiosis- or immobilization stress-induced anxiety, depression, and colitis in mice

  • Yoon-Jung Shin;Dong-Yun Lee;Joo Yun Kim;Keon Heo;Jae-Jung Shim;Jung-Lyoul Lee;Dong-Hyun Kim
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.255-264
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    • 2023
  • Background: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice. Methods: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests. Results: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF+NeuN+ cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased. Conclusion: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.

Call Admission Control in Wireless Ad-hoc Networks with Multiple Channels and Radios

  • Ko, Sung-Won
    • Journal of the Korean Institute of Illuminating and Electrical Installation Engineers
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    • v.21 no.4
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    • pp.104-114
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    • 2007
  • In this paper, an Ad-hoc Routing Protocol that works in wireless Ad-hoc communication networks with multiple radios and multiple channels and that controls call admission based on bandwidth measurement is proposed. Unlike the conventional Ad-hoc node with a single radio using a single channel, an Ad-hoc node of the protocol proposed, the MCQosR(Multiple Channel Quality of Service Routing), has multiple radios and uses multiple channels, which allows full duplex transmission between wireless Ad-hoc nodes, and reduces intra interference on the route. Also, a fixed channel only for reception at each node enables the estimation of the available bandwidth, which is used to control the call admission for QoS provision. The performance of the MCQosR was verified by simulation.