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miR-9 Modulates Osteosarcoma Cell Growth by Targeting the GCIP Tumor Suppressor

  • Zhu, Shao-Wen;Li, Jian-Peng;Ma, Xin-Long;Ma, Jian-Xiong;Yang, Yang;Chen, Yang;Liu, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권11호
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    • pp.4509-4513
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    • 2015
  • Osteosarcoma is the most common primary bone tumor in humans, especially in childhood. However, the genetic etiology for its pathogenesis remains elusive. It is known that microRNAs (miRNAs) are involved in the development of tumor progression. Here we show that microRNA-9 (miR-9) is a potential oncogene upregulated in osteosarcoma cells. Knockdown of miR-9 in osteosarcoma resulted in suppressed colony formation and cell proliferation. Further study identified GCIP, a Grap2 and cyclin D interacting protein, as a direct target of miR-9. In addition, GCIP overexpression activated retinoblastoma 1 (Rb) and suppressed E2F transcriptional target expression in osteosarcoma cells. Moreover, GCIP depletion reversed miR-9 knockdown induced colony formation and cell proliferation suppression. In sum, these results highlight the importance of miR-9 as an oncogene in regulating the proliferation of osteosarcoma by directly targeting GCIP and may provide new insights into the pathogenesis of osteosarcoma.

Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells

  • Zhao, Song-Feng;Zhang, Xiao;Zhang, Xiao-Jian;Shi, Xiu-Qin;Yu, Zu-Jiang;Kan, Quan-Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권8호
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    • pp.3363-3368
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    • 2014
  • Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. Materials and Methods: SKOV3 ovarian cancer cells were treated with curcumin ($10-60{\mu}M$) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. Results: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. Conclusions: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.

Enantio-Selective Inhibition of (1R,9S)- and (1S,9R)-$\beta$-Hydrastines on Dopamine Biosynthesis in PC12 Cells

  • Yin, Shou-Yu;Kim, Yu-Mi;Lee, Jae-Joon;Jin, Chun-Mei;Yang, You-Jong;Kang, Min-Hee;Lee, Myung-Koo
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.138.2-139
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    • 2003
  • The inhibitory effects of (1R, 9S)- and (1S, 9R)-enantiomers of $\beta$-hydrastine (BHS) on dopamine biosynthesis in PC12 cells were investigated. (1R, 9S)-BHS decreased the intracellular dopamine content with the $IC_{50}$ value of 14.3 $\mu\textrm{M}$ at 24 h, but (1S, 9R)-BHS did not. In these conditions, (1R, 9S)-BHS inhibited TH activity mainly in a concentration-dependent manner(33% inhibition at 20 $\mu\textrm{M}$) and decreased TH mRNA level. (omitted)

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Roy's Adaptation Model에 의한 모성영역에서의 간호진단 확인연구 (A Study for Identification of Nursing Diagnosis using the Roy's Adaptation Model in Maternity Unit)

  • 조정호
    • 대한간호
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    • 제33권3호
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    • pp.79-91
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    • 1994
  • The purpose of this study was to identify the meaningful nursing diagnosis in maternity unit and to suggest formally the basal data to the nursing service with scientific approach. The subject for this paper were 64 patients who admitted to Chung Ang University Hospital, Located in Seoul, from Mar. 10, to July 21, 1993. The results were as follows: 1. The number of nursing diagnosis from 64 patients were 892 and average number of nursing diagnosis per patient was 13.9. 2. Applying the division of nursing diagnosis to Roy's Adaptation Model, determined nursing diagnosis from the 64 patients were 621 (69.6%) in physiological adaptation mode and (Comfort, altered r/t), (Injury, potential for r/t), (Infection, potential for r/t), (Bowel elimination, altered patterns r/t), (Breathing pattern, ineffective r/t), (Nutrition, altered r/t less than body requirement) in order, and 139 (15.6%) in role function mode, (Self care deficit r/t), (Knowledge deficit r/t), (Mobility, impaired physical r/t) in order, 122 (13.7%) in interdependence adaptation mode, (Anxiety r/t), (Family Process, altered r/t) in order, 10(1.1%) in self concept adaptation mode, (Powerlessness r/t), (Grieving, dysfunctional r/t) in order. 3. Nursing diagnosis in maternity unit by the medical diagnosis, the average hospital dates were 3.8 days in normal delivery and majority of used nursing diagnosis, (Comfort, altered r/t) 64.6%, (Self care deficit r/t) 13.6% in order, and the average hospital dates were 9.6 days in cesarean section delivery and majority of used nursing diagnosis, (Comfort, altered r/t) 51.6%, (Self care deficit r/t) 15.2%, (Infection, potential for r/t) 9.9%, (Injury, potential "for r/t) 8.1%, (Anxiety r/t) 5.0%, (Mobility, impaired physical r/t) 3.3% in order, and the average hospital dates were 15.8days in preterm labor and majority of used nursing diagnosis, (Comfort, altered r/ t), (Anxiety r/t), (Injury, potential for r/t) in order, and the average short-term hospital dates were 2.5days, long-term hospital dates were 11.5days in gynecologic diseases and majority of used nursing diagnosis, (Comfort, altered r/t). (Self care deficit r/t), (Injury, potential for r/t), (Infection, potential for r/t) in order.

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The Effect of Thoracoscopic Sympathicotomy at the Fourth Rib (R4) for the Treatment of Palmar and Axillary Hyperhidrosis

  • Kim, Jae-Bum;Park, Chang-Kwon;Kum, Dong-Yoon
    • Journal of Chest Surgery
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    • 제44권2호
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    • pp.154-158
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    • 2011
  • Background: Video-assisted thoracic sympathicotomy plays an important for the treatment of essential hyperhidrosis. Patients are usually satisfied with the surgical outcome at the early post-operative period, but suffer recurrence and compensatory sweating in the late post-operative period. There are many sympathicotomy methods to minimize recurrence and compensatory sweating. We compared the outcome of sympathicotomy methods above the third rib (R3) and the fourth rib (R4) with regards to symptoms, satisfaction, recurrence, and compensatory palmar and axillary hyperhydrosis. Materials and Methods: From January 1999 to April 2009, 39 cases of thoracoscopic sympathicotomy at the third rib (R3), and 94 cases of thoracoscopic sympathicotomy at the fourth rib (R4) for palmar and axillary hyperhidrosis were compared for early and late post-operative satisfaction, compensatory sweating and recurrence. Results: There was no sex or age difference between groups. Early satisfaction was 94.9% and 98.9% in the R3 group and R4 group, respectively. There was no difference in early satisfaction (94.9% in R3 and 98.9% in R4), late satisfaction (84.6% in R3 and 89.4% in R4), or recurrence (17.9% in R3 and 17.0% in R4) between groups. There was significant difference in compensatory sweating (71.8% in R3 and 33% in R4, p=0.002). Conclusion: R4 sympathicotomy demonstrated superior efficacy in the treatment of compensatory sweating compared to R3 in palmar and/or axillary hyperhidrosis.

Effects of ${\alpha}-ketol$ type oxylipin (KODA) on flowering and its application as a growth regulater

  • Yokoyama, Mineyuki
    • 한국식물생명공학회:학술대회논문집
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    • 한국식물생명공학회 2005년도 추계학술대회 및 한일 식물생명공학 심포지엄
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    • pp.27-39
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    • 2005
  • a-Ketol linolenic acid [KODA, 9,10-ketol-octadecadienoic acid, or 9-hydroxy-10 -oxo-12(Z), 15(Z)-octadecadienoic acid] was found as a stress-induced factor in Lemna paucicostata. KODA reacts with catecholamines to generate many products that strongly induce flowering in L. paucicostata, although KODA itself was inactive. KODA contains an asymmetric carbon at the 9-position in the molecule; the 9-hydroxyl group is predominantly 9R, with an enantiomeric excess of 40% (70% 9R and 30% 9S). We analyzed two major products of the reaction between KODA and norepinephrine, named FN1 and FN2. FN1 was identified as a tricyclic a-ketol fatty acid, 9(R)-11-{(2'R,8’R,10'S,11'S)-2',8'-dihydroxy-7'-oxo-11'-[(Z)-2-pentenyl]-9'-oxa-4'-azatricyclo[6.3.1.01.5]dodec-5'en-10'-yl}-9-hydroxy-10-oxoundecanoic acid. FN2 was the C-9 epimer of FN1. FN1 was derived from 9R-type KODA and FN2 from 9S-type. FN1 showed strong flower-inducing activity, but FN2 was inactive. Pharbitis nil (violet) is a typical short-day plant; flowering can be induced by exposing a seedling cultivated under continuous light to a single 16-h dark period. We analyzed endogenous KODA levels and showed that they were closely related to flower induction: KODA sharply increased in the later part of a 16-h dark period, on the other hand, it failed to increase in the night-break experiment. In addition to it, KODA increased transiently in immature flower buds in all the plants we examined, including P. nil. No such increase of KODA was seen in foliar buds of P. nil. When KODA was sprayed on seedlings of Pharbitis, flower induction was promoted only by the (R)-form of KODA. We also found that KODA enhances flowering in garden plants such as carnations and impatienses. These phenomena indicate that KODA may be involved in flowering formationg of plants and it is potentially useful for a regulating agent for commercial plant flowering.

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효소 분해순서를 달리하여 제조한 탈지대두박효소 분해물의 이화학적 및 관능적 특성 (Physicochemical and Sensory Characteristics of Hydrolyzed Vegetable Protein Manufactured by Various Enzyme Reaction Order of Defatted Soybean Meal)

  • 신명곤;이규희
    • 한국식품영양과학회지
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    • 제45권9호
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    • pp.1279-1284
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    • 2016
  • 식물성 단백질 급원인 탈지대두박에 Flavourzyme$^{(R)}$(F), Neutrase$^{(R)}$(N), Alcalase$^{(R)}$(A), Protamex$^{(R)}$(P)의 단백질 분해효소를 작용시켰을 때 짠맛을 많이 생성하는 조건을 확인하고자 하였다. 효소처리 순서를 달리하여 제조한 enzyme hydrolyzed vegetable protein의 고형분 함량은 1차 Neutrase $^{(R)}$(N), 2차 Alcalase$^{(R)}$(A), 3차 Flavourzyme$^{(R)}$(F), 4차 Protamex$^{(R)}$(P)를 처리한 NAFP 처리구에서 5.60%로 가장 높은 값을 나타내었으나 고형분 함량에서는 효소의 처리 순서가 큰 영향을 미치지 않는 것을 알 수 있었다. 아미노태질소 함량은 24개의 처리구들 중에서 ANFP(102.76 mg%)와 APNF(102.85 mg%) 처리구가 통계적으로 높은 값을 나타내었다. 정량묘사분석 결과 짠맛은 PNFA(11.81) 처리구가 통계적으로 유의차를 나타내며 높은 값을 나타내었고, NPAF(10.14), FPNA(10.00), APNF(9.80), NAFP(9.76), AFNP(9.57), APFN(9.52), NPFA(9.50) 처리구가 처리구간에 통계적으로 유의차를 나타내지 않으며 다음으로 높은 값을 나타내었다. 감칠맛은 모든 처리구에서 통계적으로 유의차를 나타내지 않았다. 쓴맛 후미는 AFPN(5.67) 처리구가 가장 높은 값을 나타내었으며 FAPN(2.38), PNAF(2.62), NAPF(2.48) 처리구에서 낮은 값을 나타내었다. 관능평가 묘사분석 결과를 주성분 분석한 결과 PNFA, NAFP, APFN, NPAF, FPNA, NPFA, APNF 처리구는 짜고 감칠맛 나는 맛을 낼 수 있는 효소처리법이었다. 따라서 이들 효소의 처리 순서가 짜고 감칠맛 나는 식물단백효소 분해물의 제조에 바람직한 방법임을 알 수 있었다.

Expression of MiR200a, miR93, Metastasis-related Gene RECK and MMP2/MMP9 in Human Cervical Carcinoma - Relationship with Prognosis

  • Wang, Ling;Wang, Qiang;Li, He-Lian;Han, Li-Ying
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권3호
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    • pp.2113-2118
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    • 2013
  • Aim and Background: Cervical cancer remains the third most common cancer in women globally after breast and colorectal cancer. Well-characterized biomarkers are necessary for early diagnosis and to predict metastatic progression and effective therapy. MiRNAs can regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or degradation in tumor cells. The present study was conducted to assess expression of miR93, miR200a, RECK, MMP2, MMP9 in invasive cervical carcinoma, and analyze their clinical significance. Method: A total of 116 patients with invasive cervical carcinoma and 100 patients undergoing hysterectomy for benign lesions were retrospectively examined. Quantitative real-time PCR was performed to determine expression of miR93 and miR200a while RECK, MMP2, MMP9 and MVD were assessed by immunohistochemical staining. Results: Cervical carcinoma patients demonstrated up-regulation of miR-93, miR-200a, MMP2 and MMP9, with down-regulation of RECK as compared to benign lesion tissues. RECK was significantly inversely related to invasion and lymphatic metastasis. The 5-year survival rate for patients with strong RECK expression was significantly higher than that with weakly expressing tumors. Conclusion: MiR-93 and miR-200a are associated with metastasis and invasion of cervical carcinoma. Thus together with RECK they are potential prognostic markers for cervical carcinoma. RECK cooperating with MMP2, MMP9 expression is a significant prognostic factor correlated with long-term survival for patients with invasive cervical carcinoma.

BaCe$_{0.9}$R$_{0.1}$O$_3$-$\delta$(R=La, Yb, Al)계 페롭스카이트 상의 전기적 특성 (Electrical Characteristics of BaCe$_{0.9}$R$_{0.1}$O$_3$-$\delta$(R=La, Yb, Al) Based Perovskite Phase)

  • 최순목;김신;이홍림
    • 한국세라믹학회지
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    • 제36권1호
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    • pp.69-76
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    • 1999
  • BaCeO3 페롭스카이트 구조의 Ce4+ 자리에 3가의 양이온 (La3+, Yb3+, Al3+)을 10 mol% 첨가하여 열처리한 후 전기적 특성을 관찰하였다. 전기전도도 측정 결과 모든 조성에서 질소분위기에서 측정한 경우보다 대기 중에서 측정한 경우의 전기전도도가 높게 측정되었으며 이러한 경향은 온도가 높아질수록 두드러졌다. 전기전도도는 BaCe0.9Yb0.1O3-$\delta$조성에서 가장 높았고 BaCe0.9Al0.9O3-$\delta$ 조성에서 가장 낮았다. proton의 수송율(transference number)을 기전력 측정법을 통해 비교한 결과 Al을 첨가한 조성에서 모든 온도에 걸쳐 가장 높은 proton의 수송율을 얻을 수 있었다.

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On Fuzzy α-Weakly r-Continuous Mappings

  • Min, Won-Keun
    • International Journal of Fuzzy Logic and Intelligent Systems
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    • 제9권3호
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    • pp.228-231
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    • 2009
  • In this paper, we introduce the concept of fuzzy $\alpha$-weakly r-continuous mapping on a fuzzy topological space and investigate some properties of such a mapping and the relationships among fuzzy $\alpha$-weakly r-continuity, fuzzy r-continuity and fuzzy weakly r-continuity.