• Title/Summary/Keyword: CBX

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Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis

  • Kim, Hyun Jeong;Park, Jin Woo;Kang, Joo-Young;Seo, Sang-Beom
    • Molecules and Cells
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    • v.44 no.7
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    • pp.444-457
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    • 2021
  • Although the mechanism of chronic myeloid leukemia (CML) initiation through BCR/ABL oncogene has been well characterized, CML cell differentiation into erythroid lineage cells remains poorly understood. Using CRISPR-Cas9 screening, we identify Chromobox 8 (CBX8) as a negative regulator of K562 cell differentiation into erythrocytes. CBX8 is degraded via proteasomal pathway during K562 cell differentiation, which activates the expression of erythroid differentiation-related genes that are repressed by CBX8 in the complex of PRC1. During the differentiation process, the serine/threonine-protein kinase PIM1 phosphorylates serine 196 on CBX8, which contributes to CBX8 reduction. When CD235A expression levels are analyzed, the result reveals that the knockdown of PIM1 inhibits K562 cell differentiation. We also identify TRIM28 as another interaction partner of CBX8 by proteomic analysis. Intriguingly, TRIM28 maintains protein stability of CBX8 and TRIM28 loss significantly induces proteasomal degradation of CBX8, resulting in an acceleration of erythroid differentiation. Here, we demonstrate the involvement of the CBX8-TRIM28 axis during CML cell differentiation, suggesting that CBX8 and TRIM28 are promising novel targets for CML research.

Effects of Carbenoxolone and P2X recepter antagonist combined therapy on oral neuropathic pain in rat (신경병증 통증 모델에서 Carbenoxolone과 P2x receptor 길항제의 효과)

  • Ku, In-Young;Moon, Seon-Jeong;Ka, Kyung-Hwan;Park, Min-Kyoung
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.2
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    • pp.123-128
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    • 2016
  • The study was conducted to confirm the analgesic effects of the Carbenoxolone(CBX)and P2X receptor antagonist(iso-PPADS), which separates the gap junction in the facial neuropathic pain model. The experiment used white male Sprague-Dawley rats (240~280g). The second left molars on the lower jaw was extracted to induce facial neuropathic pain, and small dental implants were implanted to induce damage to the inferior alveolar nerve. When CBX was injected twice daily to the abdominal cavity, a significant analgesic effect at 5ug/kg was observed(p<0.05). In addition, when iso-PPADS was injected twice daily into the abdominal cavity, a significant analgesic reaction was observed at $25{\mu}g/kg$(p<0.05). When the two drugs were injected together at a low concentration, in which they did not display an effect, they displayed a significant analgesic reaction at CBX 1ug/kg and iso-PPADS 2.5ug/kg(p<0.05). When a gap injunction block using a low concentration of CBX and a low concentration P2X receptor antagonist was injected together, the pain suppressing effect was observed against the orofacial neuropathic pain mechanism. These results make it possible to determine that the gap junction block using CBX and the injection of the P2X receptor antagonist plays an important role in the pain management of the facial region.

업계소식

  • Korea Electronics Association
    • Journal of Korean Electronics
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    • v.5 no.5
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    • pp.104-108
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    • 1985
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Quantifiable Downregulation of Endogenous Genes in Agaricus bisporus Mediated by Expression of RNA Hairpins

  • Costa, Ana S.M.B.;Thomas, D. John I.;Eastwood, Daniel;Cutler, Simon B.;Bailey, Andy M.;Foster, Gary D.;Mills, Peter R.;Challen, Michael P.
    • Journal of Microbiology and Biotechnology
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    • v.19 no.3
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    • pp.271-276
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    • 2009
  • Functional gene studies in the cultivated white button mushroom Agaricus bisporus have been constrained by the absence of effective gene-silencing tools. Using two endogenous genes from A. bisporus, we have tested the utility of dsRNA hairpin constructs to mediate downregulation of specific genes. Hairpin constructs for genes encoding orotidine 5'-monophosphate decarboxylase (URA3) and carboxin resistance (CBX) were introduced into A. bisporus using Agrobacteriummediated transfection. Although predicted changes in phenotype were not observed in vitro, quantitative-PCR analyses indicated unambiguously that transcripts in several transformants were substantially reduced compared with the non-transformed controls. Interestingly, some hairpin transformants exhibited increased transcription of target genes. Our observations show that hairpin transgenic sequences can mediate downregulation of A. bisporus endogenous genes and that the technology has the potential to expedite functional genomics of the mushroom.

핵연료내 결정립 외부 공극의 상호연결분률 예측용 정육각형 퍼콜레이션 모델

  • 김한철;이종인;조규성
    • Proceedings of the Korean Nuclear Society Conference
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    • 1996.11b
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    • pp.500-505
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    • 1996
  • 고온의 정상상태에서 조사된 후 재조직(restructuring)과 균열(cracking)이 일어난 핵연료 내에서 결정립 외부 공극의 을 결정할 수 있는 퍼콜레이션(Percolation) 모델을 개발하였다. 핵연료 펠렛은 다수의 작은 정육각형 결정립들로 구성된 큰 정육각형으로 모의한다. 핵연료봉은 형상과 열적 특성이 다른 네 개의 영역으로 구분하고 각 경계 위치를 임계온도로부터 계산한다. 공극의 상호연결분율은, 몬테카를로 방법으로써 싸이트(Site)의 채워짐 여부를 점검하고 Hoshen-Kopelman 방법으로써 자유 공간에 연결된 클러스터(Cluster)에 포함된 싸이트들의 수를 계산하여 채워진 싸이트의 총 개수에 대한 연결 싸이트들의 개수의 비로써 구한다. AECL-2230, CBX 핵연료봉 실험의 기체 방출분율 자료에 대하여, FASTGRASS 코드의 상호연결분율 함수를 영역별로 계산한 상호연결분율로 대치하여 계산한 결과와 비교하였다. 균열과 재조직은 핵분열 기체 방출에 상당히 영향을 미치는 것으로 나타났다. 이 모델의 주요 장점은 결정립계에서의 상호연결현상을 단순 상호연결분율보다 좀더 사실적으로 모의하며 결정립의 성장과 균열을 고려할 수 있다는 점이다.

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Gene Expression Profile in Carpal Tunnel Syndrome Patients

  • Kim, Hye-Won;Kim, Ki-Nam;Seo, Sang-Hui;Lee, Seung-Ho;Sohn, Sung-Hwa;Kim, Yu-Ri;HaLee, Young-Mie;Shim, Jae-Sun;Ahn, Duck-Sun;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
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    • v.2 no.4
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    • pp.266-272
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    • 2006
  • Carpal tunnel syndrome (CTS) is one of the most common disorders by under pressure of the median nerve at the wrist in these days. However, pathological mechanism of CTS is unknown. We carried out this study to identify the changes of gene expression and to evaluate possible mechanism in CTS. 120 CTS patients and 30 control patients were included in this study. Patients with a history of diabetes, hypertension, thyroid diseases, and arthritis were excluded. CTS patients were divided to three experimental groups-Mild, Moderate, and Severe group-according to elecrodiagnosis. Radioactive cDNA microarrays (Nylon membrane including 1,152 genes) were used to examine the difference of gene expression profile in CTS. We identified up-regulated genes by more than 2.0 value of z-ratio, and down-regulated genes by less than-2.0 value of z-ratio. 20 genes such as the ITGAL, ITGAM, PECAM1, VIL2, TGFBR2, RAB7, RNF5 and NFKB1 were up-regulated, and 28 genes such as PRG5, CASP8, CDH1, IGFBP5, CBX3, HREV107, PIN, and WINT2 were down-regulated. These genes were related with TGF beta signaling pathway, NF-Kb signaling pathway, antiapoptotic pathway and T cell receptor signaling pathway. However, there were no differences in gene expression profiles according to severities of symptoms. We suggest that CTS could be related with proinflammatory mechanism and antiapoptotic mechanism.

Comparison of the Quantitative Values of C-14 and C-13 UBT to Reflect the Presence and Degree of Ongoing Helicobacter pylori Infection (Helicobacter pylori 감염 유무와 정도 반영에 대한 C-14와 C-13 요소호기검사 정량치 비교)

  • Lim, Seok-Tae;Kim, Dong-Wook;Jeong, Hwan-Jeong;Sohn, Myung-Hee
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.3
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    • pp.229-234
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    • 2008
  • Purpose: A urea breath test (UBT) using C-14 or C-13 has been developed for identifying Helicobacter (H) pylori infection on the basis of urease production with release of labeled $CO_2$. We investigated if the C-14 and C-13 UBT have the difference to reflect the presence and degree of H. pylori infection detected by gastro-duodenoscopic biopsies (CBx) in the same patients. Materials and methods: Thirty eight patients (M:F = 28:10, age $53.4{\pm}13.0$ yrs) with upper gastrointestinal symptoms such as indigestion, gastric fullness or pain consecutively underwent C-14 UBT, GBx and C-13 UBT within one week before medications. For the C-14 UBT, a single breath sample was collected at 10 minutes after ingestion of C-14 urea (37 KBq) capsule and counting was done in a liquid scintillation counter for 1 minute, and the results were classified as positive (${\ge}$ 200 dpm), intermediate (50-199 dpm) or negative (50 dpm). For the C-13 UBT, the results were classified as positive (${\ge}2.5\%_{\circ}$) or negative ($<2.5\%_{\circ}$). The results of GBx with Giemsa stain were graded 0 (normal) to 4 (diffuse) according to the distribution of H. pylori by the Wyatt method. We compared C-14 UBT and C-13 UBT results with GBx grade as a gold standard. Results: The prevalence of H. pylori infection by GBx with Giemsa stain was 25/38 (65.8%). In the assessment of the presence of H. pylori infection, the C-14 UBT global performance yielded sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 92.0%, 92.3%, 95.8%, 91.7% and 92.1%, respectively. However, the C-13 UBT had sensitivity, specificity, PPV, NPV and accuracy of 96.0%, 84.6%, 92.3%, 91.7% and 92.1%, respectively. The more significant correlation in C-14 than C-13 UBT (r=0.948 vs r=0.819, p <0.001) was found between the value of UBT and the grade of distribution of H. pylori infection. Conclusion: We conclude that the diagnostic performance between C-14 and C-13 UBT to detect H. pylori infection is not significantly different, but the value of C-14 UBT more significantly reflects the degree of bacterial distribution.