• Title/Summary/Keyword: CtBP2

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NSM00158 Specifically Disrupts the CtBP2-p300 Interaction to Reverse CtBP2-Mediated Transrepression and Prevent the Occurrence of Nonunion

  • Chen, Xun;Zhang, Wentao;Zhang, Qian;Song, Tao;Yu, Zirui;Li, Zhong;Duan, Ning;Dang, Xiaoqian
    • Molecules and Cells
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    • v.43 no.6
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    • pp.517-529
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    • 2020
  • Carboxyl-terminal binding proteins (CtBPs) are transcription regulators that control gene expression in multiple cellular processes. Our recent findings indicated that overexpression of CtBP2 caused the repression of multiple bone development and differentiation genes, resulting in atrophic nonunion. Therefore, disrupting the CtBP2-associated transcriptional complex with small molecules may be an effective strategy to prevent nonunion. In the present study, we developed an in vitro screening system in yeast cells to identify small molecules capable of disrupting the CtBP2-p300 interaction. Herein, we focus our studies on revealing the in vitro and in vivo effects of a small molecule NSM00158, which showed the strongest inhibition of the CtBP2-p300 interaction in vitro. Our results indicated that NSM00158 could specifically disrupt CtBP2 function and cause the disassociation of the CtBP2-p300-Runx2 complex. The impairment of this complex led to failed binding of Runx2 to its downstream targets, causing their upregulation. Using a mouse fracture model, we evaluated the in vivo effect of NSM00158 on preventing nonunion. Consistent with the in vitro results, the NSM00158 treatment resulted in the upregulation of Runx2 downstream targets. Importantly, we found that the administration of NSM00158 could prevent the occurrence of nonunion. Our results suggest that NSM00158 represents a new potential compound to prevent the occurrence of nonunion by disrupting CtBP2 function and impairing the assembly of the CtBP2-p300-Runx2 transcriptional complex.

Post-Carotid Endarterectomy Cerebral Hyperperfusion Syndrome : Is It Preventable by Strict Blood Pressure Control?

  • Kim, Kyung Hyun;Lee, Chang-Hyun;Son, Young-Je;Yang, Hee-Jin;Chung, Young Sub;Lee, Sang Hyung
    • Journal of Korean Neurosurgical Society
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    • v.54 no.3
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    • pp.159-163
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    • 2013
  • Objective : Cerebral hyperperfusion syndrome (CHS) is a serious complication after carotid endarterectomy (CEA). However, the prevalence of CHS has decreased as techniques have improved. This study evaluates the role of strict blood pressure (BP) control for the prevention of CHS. Methods : All 18 patients who received CEA from February 2009 through November 2012 were retrospectively reviewed. All patients were routinely managed in an intensive care unit by a same protocol. The cerebral perfusion state was evaluated on the basis of the regional cerebral blood flow (rCBF) study by perfusion computed tomography (pCT) and mean velocity by transcranial doppler (TCD). BP was strictly controlled (<140/90 mm Hg) for 7 days. When either post-CEA hyperperfusion (>100% increase in the rCBF by pCT or in the mean velocity by TCD compared with preoperative values) or CHS was detected, BP was maintained below 120/80 mm Hg. Results : TCD and pCT data on the patients were analyzed. Ipsilateral rCBF was significantly increased after CEA in the pCT (p=0.049). Post-CEA hyperperfusion was observed in 3 patients (18.7%) in the pCT and 2 patients (12.5%) in the TCD study. No patients developed clinical CHS for one month after CEA. Furthermore, no patients developed additional neurological deficits related to postoperative cerebrovascular complications. Conclusion : Intensive care with strict BP control (<140/90 mm Hg) achieved a low prevalence of post-CEA hyperperfusion and prevented CHS. This study suggests that intensive care with strict BP control can prevent the prevalence of post-CEA CHS.

A Morphometric Aspect of the Brachial Plexus in the Periclavicular Region

  • Lee, Jung-Pyo;Chang, Jae-Chil;Cho, Sung-Jin;Park, Hyung-Ki;Choi, Soon-Kwan;Bae, Hack-Gun
    • Journal of Korean Neurosurgical Society
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    • v.46 no.2
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    • pp.130-135
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    • 2009
  • Objective: The purpose of this study was to determine the normal morphometric landmarks of the uniting and dividing points of the brachial plexus (BP) in the periclavicular region to provide useful guidance in surgery of BP injuries. Methods: A total of 20 brachial plexuses were obtained from 10 adult, formalin-fixed cadavers. Distances were measured on the basis of the Chassaignac tubercle (CT), and the most lateral margin of the BP (LMBP) crossing the superior and inferior edge of the clavicle. Results: LMBP was located within 25 mm medially from the midpoint in all subjects. In the supraclavicular region, the upper trunk uniting at 21$\pm$7 mm from the CT, separating into divisions at 42$\pm$5 mm from the CT, and dividing at 19$\pm$4 mm from the LMBP crossing the superior edge of the clavicle. In the infraclavicular region, the distance from the inferior edge of the clavicle to the musculocutaneous nerve (MCN) origin was 49$\pm$12 mm, to the median nerve origin 57$\pm$7 mm, and the ulnar nerve origin 48$\pm$6 mm. From the lateral margin of the pectoralis minor to the MCN origin the distance averaged 3.3$\pm$10 mm. Mean diameter of the MCN was 4.3$\pm$1.1 mm (range, 2.5-6.0) in males (n = 6), and 3.1$\pm$1.5 mm (range, 1.6-4.0) in females (n = 4). Conclusion: We hope these data will aid in understanding the anatomy of the BP and in planning surgical treatment in BP injuries.

The Virulence Factors of Vibrio spp. (비브리오의 병원성 인자에 관한 연구)

  • Oh, Yang-Hyo;Kim, Yung-Bu;Park, Young-Min;Kim, Min-Jung;Cha, Mi-Sun;Kim, Young-Hee;Lim, Eun-Gyoung
    • The Journal of the Korean Society for Microbiology
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    • v.34 no.6
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    • pp.513-518
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    • 1999
  • A total of 113 Vibrio sp. strains were examined for plasmid content which were subjected to digestion with restriction enzymes. About the 55% Vibrio spp. have the plasmid more than one. Most of these plasmid various derivatives ranged from $2.4\;kb{\sim}23\;kb$, especially two strains of V. mimicus and one strain of V. furnissii carried one high-molecular weight plasmid (molecular weight ranging between $70\;kb{\sim}100\;kb$). Results of restriction analysis for plasmid of this three strains were by no means the rule. For detection of tdh and ctx gene, the virulence factor involved in the pathogenesis, we carried out the TDH and CT assay, PCR amplification, and hybridization. A total 11 strains were produced TDH, involved in 9 strains of V. parahaemolyticus and 1 strain of V. alginolyticus from clinical isolates and 1 strains of V. mimicus from environmental isolates. In the experiments of tdh gene detection, in all, 3 strains of V. parahaemolyticus from clinical isolates and 2 strains from environmental isolates could be successfully amplified in 400 bp by PCR. The PCR results were consistent with DNA hybridization tests. In the experiments of CT assay, in all, 3 strains of V. cholerae from clinical isolate and 1 strain of V. cholerae from environmental isolates were observed CT-producing. These CT-producing strains amplified in 302 bp by PCR for the detection of ctx gene. All CT-producing strains hybridized with digoxigenin-labeled DNA probe, while CT-negative strains did not hybridize. Also hybridization tests results for detection of ctx gene consistent with PCR.

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Evaluation of mandibular cortical bone ratio on computed tomography images in patients taking bisphosphonates

  • Koo, Chul-Hong;Lee, Jae-Hoon
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.40
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    • pp.17.1-17.7
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    • 2018
  • Background: Bisphosphonate (BP) has the ability to thicken the cortical bone. In addition, it has been reported that the cortical bone thickened by BP has relation to the medication-related osteonecrosis of the jaw (MRONJ). Therefore, the objective of this article is to analyze the ratio as well as thickness of cortical bone in the mandible using computed tomography (CT) and to evaluate it as the predictive factor of MRONJ. Methods: The thickness of the cortical bone was measured on a paraxial view of the CT showing the mental foramen in 95 patients: 33 patients with MRONJ (3 males, 30 females), 30 patients taking BP without MRONJ (2 males, 28 females), and 32 controls (9 males, 28 females). Also, the ratios of the cortical bone to the total bone were obtained using the measured values. Based on these results, we compared the difference of mandibular cortical bone ratio between the three groups. Results: The average cortical bone thickness was measured as 3.81 mm in patients with MRONJ, 3.39 mm in patients taking BP without MRONJ, and 3.23 mm in controls. There was only a significant difference between patients with MRONJ and controls (P < 0.05). On the other hand, the average mandibular cortical bone ratio was measured as 37.9% in patients with MRONJ, 27.9% in patients taking BP without MRONJ, and 23.3% in controls. There was a significant difference between all groups (P < 0.05). Conclusion: The mandibular cortical bone ratio is large in order of patients with MRONJ, patients taking BP without MRONJ, and controls. This result suggests that the mandibular cortical bone ratio would be very useful to predict the development of MRONJ.

The Expression of Matrix Metalloprotease 20 is Stimulated by Wild Type but not by 4 bp- or 2 bp-Deletion Mutant DLX3

  • Park, Hyun-Jung;Ryoo, Hyun-Mo;Woo, Kyung-Mi;Kim, Gwan-Shik;Baek, Jeong-Hwa
    • International Journal of Oral Biology
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    • v.34 no.1
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    • pp.21-28
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    • 2009
  • Mutations in DLX3 are associated with both autosomal dominant hypoplastic hypomaturation amelogenesis imperfecta (ADHHAI) and tricho-dento-osseous (TDO) syndrome. ADHHAI is caused by a c.561_562delCT (2bp-del DLX3) mutation whereas TDO syndrome is associated with a c.571_574delGGGG (4bp-del DLX3) mutation. However, although the causal relationships between DLX3 and an enamel phenotype have been established, the pathophysiological role of DLX3 mutations in enamel development has not yet been clarified. In our current study, we prepared expression vectors for wild type and deletion mutant DLX3 products (4bp-del DLX3, 2bp-del DLX3) and examined the effects of their overexpression on the expression of the enamel matrix proteins and proteases. Wild type DLX3 enhanced the expression of matrix metalloprotease 20 (MMP20) mRNA and protein in murine ameloblast-like cells. However, neither a 4bp-del nor 2bp-del DLX3 increased MMP20 expression. Wild type DLX3, but not the above DLX3 mutants, also increased the activity of reporters containing 1.5 kb or 0.5 kb of the MMP20 promoter. An examination of protein stability showed that the half-life of wild type DLX3 protein was less than 12 h whilst that of both deletion mutants was longer than 24 h. Endogenous Dlx3 was also found to be continuously expressed during ameloblast differentiation. Since inactivating mutations in the gene encoding MMP20 are associated with amelogenesis imperfecta, the inability of 4bp-del or 2bp-del DLX3 to induce MMP20 expression suggests a possible involvement of such mutations in the enamel phenotype associated with TDO syndrome or ADHHAI.

Isolation of New Microalga, Tetraselmis sp. KCTC12236BP, and Biodiesel Production using Its Biomass (신규 미세조류 Tetraselmis sp. KCTC12236BP의 분리 및 이를 이용한 바이오디젤 제조)

  • Shin, Dong-Woo;Bae, Jae-Han;Cho, Yonghee;Ryu, Young-Jin;Kim, Z-Hun;Lim, Sang-Min;Lee, Choul-Gyun
    • Journal of Marine Bioscience and Biotechnology
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    • v.8 no.1
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    • pp.39-44
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    • 2016
  • The microalgae have been studied for a source of biodiesel production. It is important to select the microalgae, which grows rapidly in local environmental conditions such as temperature range and ingredient of local seawater. The aim of this study was isolating microalga, which has rapid growth rate and high FAME contents in wide temperature ranges, for microalgal offshore cultivation in Korea, one of the country with four distinct seasons. Firstly, we had isolated a green microalga, Tetraselmis sp. KCTC12236BP, which has faster growth rate in low temperature (5 and $10^{\circ}C$) than Tetraselmis suecica and Dunaliella tertiolecta LB999 from Young Heung Island, Incheon, Korea. This microalga was cultivated in outdoor circulated tank photobioreactor (CT-PBR). As a result, this microalga could grow in wide temperature ranges (6 to $29^{\circ}C$), outdoors. After that, the biomass was recovered, and 13.2 g biodiesel could be acquired from 110 g dry biomass. These results indicate that the isolated microalga, Tetraselmis sp. KCTC12236BP is proper to biodiesel production using outdoor cultivation in Korea for all seasons.

Mutations of TYR and MITF Genes are Associated with Plumage Colour Phenotypes in Geese

  • Wang, Ye;Li, Si-Ming;Huang, Jing;Chen, Shi-Yi;Liu, Yi-Ping
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.6
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    • pp.778-783
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    • 2014
  • The polymorphism of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) genes have been proposed to play a vital role in coat colour genesis in mammals, but their role remains ambiguous in geese at best. Here, we cloned and sequenced 1,397 bp coding region of MITF gene and a 588 bp fragment of TYR exon 1 for polymorphism analysis among 157 domestic geese showing three types of plumage colour. We detected a total of three SNPs (c.280T>C, c.345G>A, and c.369G>A) in TYR and six haplotypes (H1-H6). Among them, haplotypes H1, H2, H3, and H5 were significantly associated with white plumage trait of Zhedong White Geese. However, only diplotype H1H1 and H3H5 were significantly associated with white plumage trait of Zhedong White Geese (p<0.01). We only detected one SNP (c.1109C>T) for MITF gene and found that genotype CT and TT were significantly associated with white plumage trait of Zhedong White Geese. Briefly, our study suggested an association between polymorphisms of TYR and MITF genes and the plumage colour trait in domestic geese.

Signal Change of Iodinated Contrast Agents in MR Imaging (요오드화 조영제가 MR영상에 미치는 신호 변화)

  • Jeong, HK;Kim, Seongho;Kang, Chunghwan;Lee, Suho;Yi, Yun;Kim, Mingi;Kim, Hochul
    • Journal of the Institute of Electronics and Information Engineers
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    • v.53 no.12
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    • pp.131-138
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    • 2016
  • In this study, we tried to analyze the influence of ICM(Iodinated Contrast Media) in MR imaging compare to GBCA(Gadolinium Based Contrast Agent), and as this result we discussed whether resonable or not the protocol which is MRI scan after enhanced CT scan without proper time interval in clinical field. For this research, we assembled two phantoms. which one was iodine and another one was gadolinium. We did test two phantoms in conventional MRI scan which is T1, T2, T2 FLAIR and 3D angio. After that, quantitative analysis was progressed. The results of study were as follow : SSI(Saline's Signal Intensity) was shown as each sequences 175, 1231, 333, 37 [a.u] at iodine. and 1297, 123, 757, 232 [a.u] was recorded at gadolinium. BDEPS(the Biggest Difference of EPS) was shown as each sequences 1297, 123, 757, 232 [a.u] at iodine and 793, 6, 1495, 365 [a.u] was recorded at gadolinium. At this time, EPS(Enhancement Percentage to Saline) was shown 641.1, -90.0, 127.3, 527% at iodine and 685.1, 99.4, 365.7, 1077.4% was recorded at gadolinium. BP(BDEPS's point) was shown 900, 900, 477, 900 mmol at iodine and 4, 0.2, 0.2, 40 mmol was recorded at gadolinium. CPSS(Change Point of SI to SSI) was shown 63, 423, 63, 29 mmol at iodine and each [50, 30], [4, 0.2], [4, 1], 0.2 mmol was recorded at gadolinium. According to this research, we could not only discover the fact that was iodine could effect on MR signal, but also the pattern is different as various sequences compare to gadolinium. Therefore, we expect useful diagnostic MR image in clinical field with this quantitative data for deciding protocol regarding MRI and CT scan order.

Double Extra-anatomic Bypasses in Upper and Lower Extremities - A Report of Case - (이중성 비해부학적 우회술 치험 1례)

  • 이신영
    • Journal of Chest Surgery
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    • v.22 no.2
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    • pp.330-336
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    • 1989
  • The patient was 47-year-old male who had suffered from aphasia and hemiplegia of the right side, but mental state was alert. On physical examination, BP was 130/80 mmHg in the right arm, but not checked in the left arm. The pulses of the left common carotid, brachial, and radial arteries were not palpable. The pulses of the right femoral, popliteal, and dorsalis pedis arteries were weakly palpable. Brain CT Scan revealed cerebral infarction of the left hemisphere. Aortogram showed occlusion of the left common carotid, and the right internal carotid and common iliac arteries. Subclavian steal phenomena were observed in the delayed aortogram. Double extra-anatomic bypasses; Axillo-Axillar bypass and Femora-Femoral bypass, were performed in the local anesthesia at two stages, because of risk of major operation under general anesthesia. Postoperatively, all pulses except for pulse of the left common carotid artery were equally palpable. On discharge, the hemiplegia of the right side was improved and able to walk with assistance.

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