• Molecules and Cells
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• 제41권3호
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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.

• Journal of Yeungnam Medical Science
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• 제12권1호
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• pp.32-47
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• 1995

생쥐의 백혈병세포 L1210과 항암제에 대하여 내성이 유도된 L1210AdR, L1210VcR과 L1210Cis에서 glutathione의 농도와 glutathione의 합성 조절에 관여하는 ${\gamma}$-glutamylcysteine synthetase(GCS)와 ${\gamma}$-glutamyl transpeptidase (GGT), 세포 이물질을 축합하는데 촉매하는 glutathione S-transferase(GST)의 효소 활성도와 유전자의 발현 여부를 관찰하였다. 세포내 glutathione농도(${\mu}M/mg$ protein)는 L1210이 $0.41{\pm}0.003$, L1210AdR가 $0.73{\pm}0.006$, L1210VcR은 $1.16{\pm}0.060$, L1210Cis가 $2.19{\pm}0.282$으로 모세포에 비하여 내성세포에서 통계적으로 유의한 증가를 관찰하였다. Buthionine sulfoxamine(BSO)를 1 ${\mu}M$농도로 첨가하여 12시간 배양한 세포들에서의 glutathione농도는 L1210이 88%, L1210AdR가 85%, L1210VcR이 89%, 그리고 L1210Cis는 79%의 감소를 보였다. GCS의 활성도(nM/mg protein/min)는 L1210이 104인데 비하여 L1210AdR가 128, L1210VcR는 227, 및 L1210Cis는 212로 증가하였다. GGT의 활성도(nM/mg protein/min)는 L1210이 $2.15{\pm}0.531$이었고, L1210AdR은 $2.80{\pm}0.498$, L1210VcR은 $2.42{\pm}0.389$, 그리고 L1210Cis는 $2.98{\pm}0.623$으로 내성인 세포들에서 증가하였으며 L1210AdR과 L1210Cis에서 유의하였다. GST활성도(nM/mg protein/min)는 L1210이 $16.70{\pm}4.798$이었고, L1210AdR은 $14.51{\pm}3.402$, L1210VcR은 $19.52{\pm}4.255$, L1210Cis $17.77{\pm}4.495$로 L1210VcR과 L1210Cis가 약간의 증가를 보였으며, L1210AdR은 오히려 감소를 보였다. DNA의 slot blot에서 GCS, GGT, GST 유전자의 모세포와 내성세포간에 별다른 차이를 보이지 않았다. Northern hybridization에서 GCS는 약 4.5kb 크기의 band, GST-${\pi}$는 약 1.05kb 크기의 band를 보였으며 내성세포 모두에서 발현 증가가 관찰되었다. GGT의 경우 크기가 다른 6개의 band가 보였으며 특히 11.5 kb크기의 band에서 L1210AdR과 L1 210VcR의 발현이 증가하였으며, L1210VcR에서는 L1210과 다른 내성세포에서 보이는 1.95kb크기의 band가 보이지 않고 2.2kb 크기의 다른 band가 관찰되었다. 이상에서 L1210AdR과 L1210VcR의 내성에는 mdr1 유전자가 관여하고, L1210Cis의 내성에는 특히 glutathione이 중요하다. GCS, GGT 및 GST등의 활성도 및 유전자의 발현도 내성세포들에서 증가하였으며 이중 GCS는 내성세포내의 glutathione 합성에 가장 중요한 조절인자라 할 수 있다.

• Journal of Yeungnam Medical Science
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• 제10권2호
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• pp.432-444
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• 1993

Adriamycin과 vincristine 각각에 내성인 생쥐의 림프아세포성 백혈병세포 L1210세포의 특성과 내성관계 단백질을 찾아내고 항암제의 세포내 분포를 관찰하였다. 항암제의 내성생성은 adriamycin이 $10^{-5}M$과 $10^{-6}M$에서 자란 세포를 L1210-$AdR_5$와 $-AdR_6$로 하고 vincristine은 $10^{-6}M$과 $10^{-7}M$에서 자란 세포를 L1210-$VcR_6$와 $-VcR_7$로 하였다. 감수성세포는 L1210으로 하였다. 내성세포의 성장속도는 감수성세포에 비해 느렸으며 doubling time은 L1210가 29.7시간, L1210-$AdR_5$가 68.7시간 $-VdR_6$가 58.2시간이었다. 복합내성은 내성인자로 표기되었고 L1210-$AdR_5$는 vincristine에 대해 76.4배, $-VcR_6$는 adriamycin에 대해 98.6배로 나타냈다. 감수성세포와 내성세포의 세포막 단백질을 비교한 결과 L1210-$AdR_5$에서는 220, 158, 88 Kd의 내성관계단백질이 나타났고 $-VcR_6$에서는 158, 140 및 88Kd의 내성관계단백질이 관찰되었다. 세포막 표면단백질을 $^{125}I$로 결합시켜 자가방사선상으로 분석하였다. 세포막 표면단백질에 결합되는 $^{125}I$의 정도는 L1210에 0.95% L1210-$AdR_5$에 5.4%, $-VcR_6$에 1.7%였다. 세포막표면단백질은 L1210-$AdR_5$에서는 158, 72.8 및 42.4 Kd의 단백질, $-VcR_6$에서는 300, 158, 72.8 및 42.4 Kd의 단백질이 관찰되었다.

• 약학회지
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• 제50권4호
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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.

• Toxicological Research
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• 제32권2호
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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.

• 음성과학
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• 제15권3호
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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.

• Journal of Yeungnam Medical Science
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• 제14권1호
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• pp.67-76
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• 1997

항암제에 대한 내성은 내인성 또는 획득한 내성 모두가 암의 치료에 장애가 된다. P-당단백질을 encode하고있는 mdr1 유전자의 발현이 항암제에 대해 내성을 가지고 있는 암세포에서 많이 관찰되고 있으며, 최근에는 시험관적으로 항암제에 대한 내성이 유도된 암세포주들에서 mdr1 유전자가 발현되지 않는 암세포들이 보고되고 있다. 다제내성에 관계하는 또 하나의 유전자인 MRP 발현정도를 L1210세포와 내성인 L1210변이주들에서 조사하였으며, c-myc과 c-fos 유전자의 발현변화를 관찰하였다. RT-PCR을 시행하여 L1210, L1210AdR, L1210VcR에서 MRP 유전자발현을 확인하였으며, Northern hybridization한 결과 L1210세포에 비하여 L1210AdR은 유전자 발현이 40% 정도 감소하였으며, L12l0Cis는 90% 정도의 유전자 발현감소가 관찰되었다. c-myc과 c-fos유전자의 Northern hybridization한 결과 L1210에 비하여 L1210AdR은 발현감소가 나타났으나, L1210VcR과 L1210Cis의 경우는 오히려 발현증가가 관찰되었다.

• 대한치매학회지
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• 제16권3호
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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.

• Journal of Ginseng Research
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• 제47권2호
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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.

• 조명전기설비학회논문지
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• 제21권4호
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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.