• Journal of Applied Biological Chemistry
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• 제63권1호
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• pp.103-110
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• 2020

Objective: The objective of our study was to investigate anti-cancer effects of Danggui Liuhuang Decoction extract bioconverted by protease liquid coenzyme of Aspergillus kawachii (DLD-BE), compared to a non-bioconverted DLD extract (DLD-E) and determine the underlying mechanisms. Methods: DLD-E and DLD-BE were evaluated for their ability to modulate these signaling pathways and suppress the proliferation of human colorectal cancer (CRC) cells, HCT-116, LoVo, and HT-29. The anti-cancer effects of DLD-E and DLD-BE were measured by using proliferation and migration assays, cell cycle analysis, Western blots, and real-time PCR. Results: In this study, treatment with DLD-E and DLD-BE at concentrations of 25-100 ㎍/mL inhibited proliferation and migration in human CRC cells. DLD-BE induced apoptotic cell death and decreased COX-2 expression in HT-29 cells. The mechanisms of action included modulation of the AKT and extracellular-signal-regulated kinase signaling cascades along with inhibition of COX-2 expression. The results demonstrate novel anti-cancer mechanisms of DLD-BE against the growth of human CRC cells. Thus, we propose that DLD-BE can be developed as a more potent supplement to inhibit colorectal tumor growth and intestinal inflammation than DLD-E.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제8권2호
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• pp.207-216
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• 1997

본 연구는 반응성 애착장애(reactive attachment disorder：향후 RAD라 칭함)집단과 발달성 언어장애(developmental language disorder：향후 DLD라 칭함)집단을 대상으로 외관상 유사한 사회성 문제를 지니고 있으나, 타인과의 사회적 접촉의 시도라는 좀 더 근본적인 의사소통의 의도에서는 집단간에 어떤 차이를 보이는지 알아보기 위해 생활 연령과 언어 연령으로 두 집단을 짝지어 의사소통 의도의 빈도와 주로 사용하는 의사소통 의도의 유형 및 발달 단계를 비교하였다. 그 결과는 DLD아동의 의도 표현 방법이 RAD아동보다 세련되고 정교화 되었음을 보여 주었으며, DLD아동이 RAD아동보다 의사소통하려는 의도를 더 많이 가지고 있음을 나타냈다. 그리고 두집단이 사용하는 의사소통 의도의 내용을 살펴보았더니, DLD아동은 사회적 상호작용>공유적 주의>행동 통제의 순으로, RAD아동은 행동 통제>사회적 상호작용>공유적 주의의 순으로 의사소통하려는 의도를 나타냄으로써, 주로 사용하는 의도의 내용 범주간에도 두 집단간에 차이를 보였다. 또한, 사용한 의사소통 의도의 다양성 비교에서도 총 12가지의 의사소통 의도에서 DLD아동이 RAD아동보다 더 다양한 수의 의사소통 의도를 나타냈다. 이들 결과를 종합해 볼 때, DLD아동보다는 RAD아동에게서 의사소통의도로 잰 사회적 결함의 심각성이 더 드러났음을 알 수 있다.

• Oncology Letters
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• 제17권3호
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• pp.3589-3598
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• 2019

Colorectal cancer (CRC) is a complex disease involving numerous genetic abnormalities. One of the major characteristics of CRC is enhanced Wnt signaling caused by loss-of-function mutations in the adenomatous polyposis coli (APC) gene. Previously, it has been demonstrated that the majority of malignant phenotypes following APC deletion in adult murine small intestines could be rescued when Myc, a downstream target of the Wnt pathway, was deleted. This indicated that Myc is a critical regulator of CRC development following APC loss. Previous studies reported that cyclic adenosine 3',5'-monophosphate (cAMP) can influence the AKT/mammalian target of rapamycin (mTOR) survival pathway in cancer and Myc is a critical downstream molecule of AKT/mTOR signaling. Phosphodiesterase 4D (PDE4D), a member of the cAMP-specific PDE4 family, has been associated with drug resistance in CRC. However, the association between PDE4D and Myc remains unclear. To investigate the potential role of PDE4D in Myc regulation in CRC, the present study evaluated the expression levels of PDE4 subtypes in DLD-1 CRC cells. Additionally, the effects of PDE4 inhibitors on Myc expression and oncogenic properties were analyzed by western blot analysis, reverse transcription-quantitative polymerase chain reaction, colony formation and soft agar assays. It was demonstrated that cAMP/PDE4D signals serve a critical role in regulating Myc expression in DLD-1 CRC cells. Furthermore, PDE4D was identified to be a main hydrolyzer of cAMP and suppression of PDE4D using selective inhibitors of PDE4 increased intracellular cAMP levels, which resulted in a marked decrease in the oncogenic properties of DLD-1 cells, including colony formation, cell proliferation and anchorage-independent growth. Notably, the current data imply that cAMP represses Myc expression via the downregulation of AKT/mTOR signaling, which was abolished by high PDE4D activities in DLD-1 cells. Additionally, a natural polyphenol resveratrol in combination with forskolin elevated the concentration of cAMP and enhanced the expression of Myc and the malignant phenotype of DLD-1 cells, reproducing the effect of known chemical inhibitors of PDE4. In conclusion, the present study identified that cAMP/PDE4D signaling is a critical regulator of Myc expression in DLD-1 and possibly other CRC cells.

• Journal of Preventive Medicine and Public Health
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• 제15권1호
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• pp.47-56
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• 1982

Korean versions of British Medical Research Council (MRC), Cornell Medical Index(CMI), and American Thoracic Society 78 (ATS-DLD-78) respiratory questionaires were compared with each other, and were tested the stability, in terms of test-retest reliability, of each questions by self-administration of those to 156 medical students. The results obtained and conclusions drawn are as follow: 1. The degree of agreements between responses to the comparable questions of CMI vs MRC, and of CMI vs ATS-DLD-78 were not satisfactory. There were, however, $71{\sim}100$ per cent of agreement between responses to the questions on Cough, Wheezing, Phlegm, Breathlessness, and Chest illness of ATS-DLD-78 vs MRC questionaire. And the ATS-DLD-78 tended to yield greater number of positive responses than MRC (See Table 4). 2. All of the coefficient of stability of each questions in 3 questionaires were statistically significant, ranged $77{\sim}100$ per cent, except that of the question on episode of cough and phlegm in ATS-DLD-78 questionaire (See Table 5-1). The question is composed of two collateral conditions, 'lasting for 3 weeks or more' and 'each year'. 3. It can be insisted that the Section-B questions of CMI is not proper for use in epidemiologic survey on respiratory illness. And rather than MRC, the ATS-DLD-78 questionaire deserves to prefer to be used in epidemiologic studies on respiratory illness. 4. In question-wording, especially, of inquiring past experience, it is possible to lessen the reliability of the question that including collateral conditions such as 'the duration lasted of symptoms', and moreover, of which words are not common usage. For example, for Korean '10days' or 'half a month' is more familiar time unit rather than 'week'.

• 한국환경과학회지
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• 제23권6호
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• pp.1029-1035
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• 2014

This study was investigate the influences of wild haw (Crataegus pinnatifida $B_{UNGE}$) on lowering blood urea nitrogen (BUN) and creatinine concentrations in dyslipidemic rats. Four groups of rats were fed different diets for 5 weeks: basal diet (BD group), nondyslipidemic diet+feral haw extract (NDF group), dyslipidemic diet (DLD group), dyslipidemic diet+feral haw extract (DFH group). BUN, creatinine and uric acid concentrations were significantly higher in the DLD group than in the BD group. However, DFH group significantly lowered BUN, creatinine and uric acid concentrations compared to the DLD group. Amylase activity was significantly lower in the DLD group than in the BD group, while DFH group significantly higher compared to the DLD group. Lipase activity was also also significantly lower in the DLD group than the other group. Accordingly, these results suggest that haw extract could be effective for improving kidney function in dyslipidemic rats.

• 한국식품과학회지
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• 제36권5호
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• pp.812-817
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• 2004

한국 전통약주와 기존에 암세포주에 대한 세포독성이 보고되어 있는 알코올 음료에 대한 항종양 세포독성을 비교하기 위하여 무증자 발효 방법으로 발효시키면서 한약재를 첨가한 전통약주I과 뽕잎, 메밀 등을 첨가한 전통약주II, 비교 시료로 적포도주, 백포도주, 맥주, 일본 청주 등에 대하여 연구하였다. 각 시료에 대하여 10-80배까지 단계적으로 희석하여 DLD-1, HepG2, K562, EMT6, LLC1에 처리하였을 때, 인체유래 대장암 세포주인 DLD-1의 경우 적포도주에서만 강한 세포독성이 확인되었는데, 전통약주I의 경우 그 농축액에서 DLD-1에 대하여 적포도주와 유사한 세포독성을 확인할 수 있었다. 나머지 4종의 암세포주에서는 10-20배 희석배수에서 적포도주, 전통약주I, 전통약주II가 세포독성을 보였으나, 각 암세포주의 종류에 따라서 세포독성은 약간씩 차이를 보였다. HepG2, K562, EMT6의 경우 10배 희석배수에서 모두 비슷한 세포독성을 보인 반면에 마우스 유래 폐암세포주인 LLC1의 경우에는 전통약주I과 전통약주II의 세포독성이 적포도주보다 우수한 것을 확인하였다. 본 연구의 결과에 의하면 이러한 항암효과는 전통약주에 존재하는 미지의 약리성분이 작용하는 것으로 판단되었다.

• Journal of Pharmaceutical Investigation
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• 제34권5호
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• pp.393-399
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• 2004

For the efficient determination of activity against solid tumors, an in vitro tumor model that resembles the condition of in vivo solid tumors, is required. The purpose of this study was to establish a rapid culture method and viability assay for an in vitro 3-dimensional tumor model, multicellular spheroid (MCS). Among 12 human cancer cell lines, a few cell lines including DLD-1 (human colorectal carcinoma cells) formed fully compact MCS which was adequate for in vitro viability assay. DLD-1 MCS showed steady growth reaching $700\;{\mu}m$ diameter after 11 day culture. DLD-1 cells grown as MCS showed significant increase in $G_0/G_1$ phase compared to the monolayer cells (73.9% vs 45.7%), but necrotic regions or apoptotic cells were not observed. The cells cultured as MCS showed resistance to 5-FU (10.3 fold higher $IC_{50}$) compared to monolayers, however, tirapazamine (a hypotoxin) showed similar activity in both culture systems. In summary, MCS may be a valid in vitro model for activity screening of anticancer agents against human solid tumors and also exploitable for studying molecular markers of drug resistance in human solid tumors.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4249-4254
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• 2013

Background: Parafibromin is a protein encoded by the HRPT2 (hyperparathyroidism 2) oncosuppressor gene and its down-regulated expression is involved in pathogenesis of parathyroid, breast, gastric and colorectal carcinomas. This study aimed to clarify the effects of parafibromin expression on the phenotypes and relevant mechanisms of DLD-1 colon carcinoma cells. Methods: DLD-1 cells transfected with a parafibromin-expressing plasmid were subjected to examination of phenotype, including proliferation, differentiation, apoptosis, migration and invasion. Phenotype-related proteins were measured by Western blot. Parafibromin and ki-67 expression was detected by immunohistochemistry on tissue microarrays. Results: The transfectants showed higher proliferation by CCK-8, better differentiation by electron microscopy and ALP activity and more apoptotic resistance to cisplatin by DNA fragmentation than controls. There was no difference in early apoptosis by annexin V, capase-3 activity, migration and invasion between DLD-1 cells and their transfectants. Ectopic parafibromin expression resulted in down-regulated expression of smad4, MEKK, GRP94, GRP78, $GSK3{\beta}$-ser9, and Caspase-9. However, no difference was detectable in caspase-12 and -8 expression. A positive relationship was noted between parafibromin and ki-67 expression in colorectal carcinoma. Conclusions: Parafibromin overexpression could promote cell proliferation, apoptotic resistance, and differentiation of DLD-1 cells.

• 치위생과학회지
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• 제23권2호
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• pp.142-153
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• 2023

Background: Cognitive impairment has been reported to be closely associated with poor oral health, and the relationship is bidirectional, as older adults with poor oral health and chewing function are at a higher risk of cognitive decline (CD). This cross-sectional study aimed to determine whether masticatory discomfort in Korean elderly increases the risk of daily living difficulty (DLD) related to CD and whether there is a difference in risk according to gender and age. Methods: The data used were obtained from the Korean Community Health Survey (2019). The final analysis included 22,154 people aged 65 years and older who completed the survey and responded to all items on the variables used in the study. Chi-square test, trend test, and complex sample logistic regression were performed for statistical analysis, to clarify the purpose of this study. Results: As masticatory discomfort increased, the elderly's DLD tended to increase (p-for trend, p<0.001). For logistic regression, adjusting for all covariates, participants who reported masticatory discomfort as "discomfort" (adjusted odds ratio [AOR]=2.45, 95% confidence interval [CI]=2.11~3.50) and "severe discomfort" (AOR=2.95, 95% CI=2.49~3.50) had a more than a two-fold increased risk of CD-related DLD compared to participants who reported "no discomfort at all." In age-stratified analyses, elderly men aged 75~84 years and elderly women aged 65~74 years had the highest risk of developing CD-related DLD. Conclusion: Oral care interventions to improve masticatory function in older adults may slow CD and improve CD-related DLD. We hope that this study will raise awareness among caregivers and clinical professionals regarding the importance of oral care for older adults with CD.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6791-6795
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• 2013

Apoptotic and cytotoxic activity of plant extracts obtaining from naturally growing Cynara syriaca in Turkey and cultivated C cardunculus against DLD1 colorectal cancer cells was determined. Extracts from wild and cultivated Cynara species were obtained from their vegetative parts and receptacles using hexane and applied with five different dose (0.1-1 mg/ml) as well as apigenin for MTT tests for three time periods (24, 48 and 72 hours). After cells were treated with $IC_{50}$ doses for each extract total DNA and RNA were isolated for determination of the cause of cell death. From isolated RNAs, cDNA were synthesized and amplification of p21, BCL-2 and BAX gene regions was carried out. Consequently, we found that pro-apoptotic (BAX) gene expression and a cell cycle inhibitor (p21) were induced in the presence of our artichoke extracts. In contrast, anti-apoptotic BCL-2 gene expression was reduced compared to the control group. In addition DNA fragmentation results demonstrated DLD1 cell death via apoptosis.