• 제목/요약/키워드: miR-34a

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The Tumor Suppressor, p53, Negatively Regulates Non-Canonical NF-κB Signaling through miRNA-Induced Silencing of NF-κB-Inducing Kinase

  • Jang, Hanbit;Park, Seulki;Kim, Jaehoon;Kim, Jong Hwan;Kim, Seon-Young;Cho, Sayeon;Park, Sung Goo;Park, Byoung Chul;Kim, Sunhong;Kim, Jeong-Hoon
    • Molecules and Cells
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    • v.43 no.1
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    • pp.23-33
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    • 2020
  • NF-κB signaling through both canonical and non-canonical pathways plays a central role in immune responses and inflammation. NF-κB-inducing kinase (NIK) stabilization is a key step in activation of the non-canonical pathway and its dysregulation implicated in various hematologic malignancies. The tumor suppressor, p53, is an established cellular gatekeeper of proliferation. Abnormalities of the TP53 gene have been detected in more than half of all human cancers. While the non-canonical NF-κB and p53 pathways have been explored for several decades, no studies to date have documented potential cross-talk between these two cancer-related mechanisms. Here, we demonstrate that p53 negatively regulates NIK in an miRNA-dependent manner. Overexpression of p53 decreased the levels of NIK, leading to inhibition of the non-canonical NF-κB pathway. Conversely, its knockdown led to increased levels of NIK, IKKα phosphorylation, and p100 processing. Additionally, miR-34b induced by nutlin-3 directly targeted the coding sequences (CDS) of NIK. Treatment with anti-miR-34b-5p augmented NIK levels and subsequent non-canonical NF-κB signaling. Our collective findings support a novel cross-talk mechanism between non-canonical NF-κB and p53.

Upregulation of Mir-34a in AGS Gastric Cancer Cells by a PLGA-PEG-PLGA Chrysin Nano Formulation

  • Mohammadian, Farideh;Abhari, Alireza;Dariushnejad, Hassan;Zarghami, Faraz;Nikanfar, Alireza;Pilehvar-Soltanahmadi, Yones;Zarghami, Nosratollah
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8259-8263
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    • 2016
  • Background: Nano-therapy has the potential to revolutionize cancer therapy. Chrysin, a natural flavonoid, was recently recognized as having important biological roles in chemical defenses and nitrogen fixation, with anti-inflammatory and anti-oxidant effects but the poor water solubility of flavonoids limitstheir bioavailability and biomedical applications. Objective: Chrysin loaded PLGA-PEG-PLGA was assessed for improvement of solubility, drug tolerance and adverse effects and accumulation in a gastric cancer cell line (AGS). Materials and Methods: Chrysin loaded PLGA-PEG copolymers were prepared using the double emulsion method (W/O/W). The morphology and size distributions of the prepared PLGA-PEG nanospheres were investigated by 1H NMR, FT-IR and SEM. The in vitro cytotoxicity of pure and nano-chrysin was tested by MTT assay and miR-34a was measured by real-time PCR. Results: 1H NMR, FT-IR and SEM confirmed the PLGA-PEG structure and chrysin loaded on nanoparticles. The MTT results for different concentrations of chrysin at different times for the treatment of AGS cell line showed IC50 values of 68.2, 56.2 and $42.3{\mu}M$ and 58.2, 44.2, $36.8{\mu}M$ after 24, 48, and 72 hours of treatment, respectively for chrysin itslef and chrysin-loaded nanoparticles. The results of real time PCR showed that expression of miR-34a was upregulated to a greater extent via nano chrysin rather than free chrysin. Conclusions: Our study demonstrates chrysin loaded PLGA-PEG promises a natural and efficient system for anticancer drug delivery to fight gastric cancer.

Coupling of ent-Cyclic Peroxide and Ircinol A, Two Biologically Active Natural Marine Products

  • Lim, Chi-Won;Kim, Yeun-Kye;Jang, Mi-Soon;Park, Jin-Il;Park, Hee-Yeun
    • Fisheries and Aquatic Sciences
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    • v.9 no.4
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    • pp.175-178
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    • 2006
  • An acidic ent-cyclic peroxide was isolated from a sponge, Plakotis sp., and showed activity against leishmaniasis and pathogenic fungi. To improve the activity of this compound, we coupled the acidic ent-cyclic at the C1 position of ircinol A. Compound 3 exhibited significant activity against Leishmania mexican a and fungi with $IC_{50}$ values of 0.7 and $0.3-34{\mu}g/mL$, respectively. The yield of compound 3 was 98%.

A Comparison Study Between Image Analysis and Conventional Methods in the Evaluation of Asian Skin Color (아시아 피부에서 기존 미백 평가방법과 이미지 분석방법의 비교연구 (비타민 C 제형의 이온토포레시스 연구))

  • Park, Hye Kyong;Kim, Nam Soo;Moon, Tae Kee;Kim, Bora;Jung, Ho Young
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.41 no.2
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    • pp.97-103
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    • 2015
  • Until recently, the three conventional evaluation methods, which are instrumental (Chromameter$^{(R)}$ CR-400 and Mexameter$^{(R)}$ M18) and visual assessments have been used frequently for skin color evaluation. However, we took notice the potential of image analysis as a new tool to evaluate color change of skin. To reveal the reliability of the image analysis for the evaluation of whitening agents, 34 healthy female volunteers with hyperpigmentation were recruited, and the selected volunteers applied the whitening products containing Vitamin C twice a day in the morning and evening and received iontophoresis treatments once a week for 8 weeks. The changes in hyperpigmentation evaluated by Chromameter$^{(R)}$, Mexameter$^{(R)}$ and visual assessment were compared with the results from the image analysis. As with $L^*$ value trends of the analysis using Chromameter$^{(R)}$, the V value from the image analysis increased after applying the test products compared with baseline values. Furthermore, V value showed a positive correlation with $L^*$ value (r = 0.494, p < 0.01) and negative correlation with MI (r = - 0.683, p < 0.01) and VG (r = - 0.549, p < 0.01). Therefore, image analysis may be considered as an effective method to complement the limitations of visual assessment for whitening efficacy in Asians.

Synergistic Effects of Bee Venom and Natural Killer Cells on B16F10 Melanoma Cell Growth Inhibition through IL-4-mediated Apoptosis

  • Sin, Dae Chul;Kang, Mi Suk;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.34 no.1
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    • pp.1-9
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    • 2017
  • Objectives : We investigated the synergistic effects of bee venom (BV) and natural killer (NK) cells on B16F10 melanoma cell apoptosis mediated by IL-4. Methods : We performed a cell viability assay to determine whether BV can enhance the inhibitory effect of NK-92MI cells on the growth of B16F10 melanoma cells, and western blot analysis to detect changes in the expression of IL-4, $IL-4R{\alpha}$, and other apoptosis-related proteins. EMSA was performed to observe the activity of STAT6. To confirm that the inhibitory effect of BV and NK cells was mediated by IL-4, the above tests were repeated after IL-4 silencing by siRNA (50 nM). Results : B16F10 melanoma cells co-cultured with NK-92MI cells and simultaneously treated by BV ($5{\mu}g/ml$) showed a higher degree of proliferation inhibition than when treated by BV ($5{\mu}g/ml$) alone or co-cultured with NK-92MI cells alone. Expression of IL-4, $IL-4R{\alpha}$, and that of other pro-apoptotic proteins was also enhanced after co-culture with NK-92MI cells and simultaneous treatment with BV ($5{\mu}g/ml$). Furthermore, the expression of anti-apoptotic bcl-2 decreased, and the activity of STAT6, as well as the expression of STAT6 and p-STAT6 were enhanced. IL-4 silencing siRNA (50 nM) in B16F10 cells, the effects of BV treatment and NK-92MI co-culture were reversed. Conclusion : These results suggest that BV could be an effective alternative therapy for malignant melanoma by enhancing the cytotoxic and apoptotic effect of NK cells through an IL-4-mediated pathway.

Sequence Analysis of the 18S rDNA from Scallops Collected around Korean Sea (한국 주변해역 가리비로부터 분리한 18S rDNA의 염기서열 분석)

  • KIM Mi-Jung;JM Long-Guo;JIN Hyung-Joo;CHO Ji-Young;PARK Jung-Youn;CHANG Young Jin;HONG Yong-Ki
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.34 no.2
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    • pp.137-144
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    • 2001
  • Sequences of partial 18S rDNA have been analyzed to elucidate genetic diversity of scallops collected around Korean sea, The scallops used in genetic comparison are Argopecten irradians concentricus, Amusium japonicum japonicum, Chlamys farreri farreri, Chlamys (Swiftopecten) swifti and Patinopecten yessoensis. The 18S rDNA sequences were aligned by Clustalx program. Phylogenetic tree was drawn by Treecon program, The scallops were divided into two groups-the Family Pectinidae containing A. japonicum japonicum and the Family Propeamussiidae containing Argopecten, Chlamys and Patinopecten genera. The Family Propeamussiidae was also divided into the Supergenera Aequipecten containing A. irradians concentricus and Supergenera Chlamys containing C. farreri farreri, C. swifti and P. yessoensis. The species of C. swifti was closer to the P. yessoensis rather than C. farreri farreri in respect to nuclear 18S rDNA sequence.

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A Convergence Study of Nurses' Incident Reporting and Perceived Safety Climate (간호사의 사건보고와 안전분위기 인지에 대한 융합연구)

  • Koh, Yu-Mi;Kim, Ju-Sung
    • Journal of the Korea Convergence Society
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    • v.9 no.4
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    • pp.443-452
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    • 2018
  • The purpose of this study was to identify the factors affecting perceived safety climate and the level of incident reporting attitude, incident reporting knowledge and safety climate. The data were collected by structured questionnaires from 240 nurses and were analyzed with descriptive statistics, t-test, ANOVA, Scheffe test, Pearson's correlation coefficients and multiple regression. The level of incident reporting attitude and incident reporting knowledge was 3.34 and 3.05. The level of safety climate was 3.25. Incident reporting knowledge and safety climate have a significant positive association with incident reporting attitude(r=.33, p<.001; r=.38, p<.001). Incident reporting knowledge was positively associated with safety climate(r=.32, p<.001). Factors influencing safety climate were incident reporting knowledge, belief in improvement and reporting intention which explained 24.7% of the variance(F=12.22, p<.001). The findings indicate that to improve incident reporting knowledge with positive attitude and safety climate should be considered as patient safety strategy and should endeavour to develop interventions for safety.

Impacts of Menstrual Attitudes, Premenstrual Syndrome and Stress on Burnout among Clinical Nurses (임상간호사의 월경태도, 월경전증후군, 스트레스가 소진에 미치는 영향)

  • Hwang, Ji-Hye;Sung, Mi-Hae
    • Women's Health Nursing
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    • v.22 no.4
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    • pp.233-240
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    • 2016
  • Purpose: The purpose of this study was to investigate factors which effect clinical nurses' exhaustion. Methods: This research was conducted targeting 140 clinical nurses. Data were collected from 18 September to 30 September 2015. Data were analyzed using the program SPSS/WIN 18.0. Descriptive statistics, t-test, ANOVA, Pearson correlation coefficient, and Stepwise multiple regression analysis were used. Results: Burnout was significantly different by age (F=7.99, p=.001), marital status (t=8.69, p=.004), department area (F=7.65, p<.001), frequency of night work in a month (F=7.65, p=<.001), and clinical career (F=3.68, p=.028). There was positive correlations between menstrual attitudes of participants and premenstrual syndrome (r=34, p<.001), menstrual attitudes and stress (r=.40, p<.001), and menstrual attitudes and burnout (r=.16, p=.031). There were positive correlations between premenstrual syndrome and stress (r=.46, p<.001), between premenstrual syndrome and burnout (r=.35, p<.001), and between stress and burnout (r=.36, p<.001). Factors influencing burnout were premenstrual syndrome (${\beta}=.335$) and age (${\beta}=.216$), with an explanatory power of 18.0%. Conclusion: There is a need to develop and apply program for reducing clinical nurses' pre-menstrual syndrome. In addition, policies are needed to allow for menstruation leave, thereby making it legal.

The Influence of Maturity Fears and Appearance Interest on Self-concept among Lower-grade Elementary School Girls with Precocious Puberty (초등학교 저학년 성조숙증 여아의 성숙불안과 신체외모 관심이 자아개념에 미치는 영향)

  • Nam, Hyun-Jeong;Choi, Mi-Young
    • Child Health Nursing Research
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    • v.26 no.2
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    • pp.181-189
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    • 2020
  • Purpose: This study explored the relationships of maturity fears and appearance interest(interest in appearance, interest in weight) with self-concept among girls with precocious puberty. Methods: The participants for this study were 120 elementary school students (8 to 10 years old) and their parents from two hospitals located in Chungcheong Province. Data were collected from January to February 2019 using self-reported questionnaires. The collected data were analyzed using descriptive statistics, the independent t-test, the Mann-Whitney U test, one-way analysis of variance, Pearson correlation coefficients, and multiple regression analysis in SPSS for Windows version 23.0. Results: Statistically significant negative correlations were found between self-concept and maturity fears (r=-.34, p<.001) and interest in weight (r=-.29, p=.001). Maturity fears were identified as a factor affecting the self-concept of girls with precocious puberty (β=-.34, p<.001). This variable explained 11.5% of the variance in the self-concept of girls who experienced precocious puberty. Conclusion: This study confirmed that maturity fears had a major influence on self-concept in girls with precocious puberty. The results of this study can be used as basic data for the development of a psychosocial nursing intervention program for girls who experience precocious puberty.

Antiviral Efficacy of a Short PNA Targeting microRNA-122 Using Galactosylated Cationic Liposome as a Carrier for the Delivery of the PNA-DNA Hybrid to Hepatocytes

  • Kim, Hyoseon;Lee, Kwang Hyun;Kim, Kyung Bo;Park, Yong Serk;Kim, Keun-Sik;Kim, Dong-Eun
    • Bulletin of the Korean Chemical Society
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    • v.34 no.3
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    • pp.735-742
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    • 2013
  • Peptide nucleic acids (PNAs) that bind to complementary nucleic acid sequences with extraordinarily high affinity and sequence specificity can be used as antisense oligonucleotides against microRNAs, namely antagomir PNAs. However, methods for efficient cellular delivery must be developed for effective use of PNAs as therapeutic agents. Here, we demonstrate that antagomir PNAs can be delivered to hepatic cells by complementary DNA oligonucleotide and cationic liposomes containing galactosylated ceramide and a novel cationic lipid, DMKE (O,O'-dimyristyl-N-lysyl glutamate), through glycoprotein-mediated endocytosis. An antagomir PNA was designed to target miR-122, which is required for translation of the hepatitis C virus (HCV) genome in hepatocytes, and was hybridized to a DNA oligonucleotide for complexation with cationic liposome. The PNA-DNA hybrid molecules were efficiently internalized into hepatic cells by complexing with the galactosylated cationic liposome in vitro. Galactosylation of liposome significantly enhanced both lipoplex cell binding and PNA delivery to the hepatic cells. After 4-h incubation with galactosylated lipoplexes, PNAs were efficiently delivered into hepatic cells and HCV genome translation was suppressed more than 70% through sequestration of miR-122 in cytoplasm. PNAs were readily released from the PNA-DNA hybrid in the low pH environment of the endosome. The present study indicates that transfection of PNA-DNA hybrid molecules using galactosylated cationic liposomes can be used as an efficient non-viral carrier for antagomir PNAs targeted to hepatocytes.