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Downregulation of JMJD2a and LSD1 is involved in CK2 inhibition-mediated cellular senescence through the p53-SUV39h1 pathway

  • Park, Jeong-Woo;Bae, Young-Seuk
    • BMB Reports
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    • 제55권2호
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    • pp.92-97
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    • 2022
  • Lysine methylation is one of the most important histone modifications that modulate chromatin structure. In the present study, the roles of the histone lysine demethylases JMJD2a and LSD1 in CK2 downregulation-mediated senescence were investigated. The ectopic expression of JMJD2a and LSD1 suppressed the induction of senescence-associated β-galactosidase activity and heterochromatin foci formation as well as the reduction of colony-forming and cell migration ability mediated by CK2 knockdown. CK2 downregulation inhibited JMJD2a and LSD1 expression by activating the mammalian target of rapamycin (mTOR)-ribosomal p70 S6 kinase (p70S6K) pathway. In addition, the down-regulation of JMJD2a and LSD1 was involved in activating the p53-p21Cip1/WAF1-SUV39h1-trimethylation of the histone H3 Lys9 (H3K9me3) pathway in CK2-downregulated cells. Further, CK2 downregulation-mediated JMJD2a and LSD1 reduction was found to stimulate the dimethylation of Lys370 on p53 (p53K370me2) and nuclear import of SUV39h1. Therefore, this study indicated that CK2 downregulation reduces JMJD2a and LSD1 expression by activating mTOR, resulting in H3K9me3 induction by increasing the p53K370me2-dependent nuclear import of SUV39h1. These results suggest that CK2 is a potential therapeutic target for age-related diseases.

영유아기 과잉치의 임상적 처치 및 micro-computed tomography 분석: 증례 보고 (Clinical Management and Micro-Computed Tomography Analysis of Supernumerary Teeth in Infancy: A Case Report)

  • 나채현;이한아;김한성;김지훈
    • 대한소아치과학회지
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    • 제49권3호
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    • pp.348-356
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    • 2022
  • 과잉치는 치판의 과도한 성장과 분화에 의해서 발생된다. 이로 인해 이소맹출, 맹출지연, 인접치의 치근 흡수, 그리고 치간이개 등의 문제가 발생할 수 있다. 영유아기에서의 과잉치는 드물며 국내에서는 거의 보고되지 않았다. 이 증례에서는 3개의 매복된 과잉치가 있는 생후 2일된 신생아에 대해 보고하고 있으며, 환자는 21개월간 추적 관찰되었다. 유치열기에 맹출된 하나의 과잉치는 14개월이 되었을 때 중등도 진정 하에 발치되었다. 발치된 과잉치에 대해 micro-computed tomography (CT) 분석을 진행하여 치근단 부위의 미세한 형태 이상을 확인하였다. 과잉치 발치 후 치간이개는 감소하였고 구강위생도 개선되었다. 조기 진단 및 치료를 통해 과잉치로 인한 합병증을 예방할 수 있다.

Floating-Harbor 증후군 환자와 쌍둥이 여동생의 치성 및 골격성 특성과 행동 양상 비교 (Dental and Skeletal Characteristics and Behavioral Aspects of the Patient with Floating-Harbor Syndrome Compared with Twin Sister)

  • 임종화;김기민;이제식;남순현;김현정
    • 대한소아치과학회지
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    • 제49권2호
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    • pp.234-240
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    • 2022
  • Floating Harbor 증후군 (FHS)은 드문 유전질환이다. 본 증례는 FHS를 가진 환아에 대해 소개하였다. 환아는 독특한 얼굴 형태, 저성장된 상악과 전돌된 하악을 동반한 심한 골격적 3급 부정교합, 결손치, 왜소치, 상악 치아의 이소맹출을 보였다. 쌍둥이 여동생은 하악 전돌을 동반한 경미한 골격성 3급 부정교합은 보였으나 결손치와 왜소치는 보이지 않았다. 높은 구개궁, 넓은 난형의 하악궁에 비해 좁은 V형의 상악궁, 역의 관계의 상하악 구치간 폭경으로 인한 구치부 반대교합이 환자의 모델 분석을 통해 확인되었다. 이러한 특성은 쌍둥이에서는 나타나지 않았다. 행동면에서 환아는 경미한 정신지체로 인해 치과 치료 중 낮은 협조도를 보였다.

Epidemiological investigation of equine hindlimb ataxia with Setaria digitata in South Korea

  • Hwang, Hyeshin;Ro, Younghye;Lee, Hyunkyoung;Kim, Jihyeon;Lee, Kyunghyun;Choi, Eun-Jin;Bae, You-Chan;So, ByungJae;Kwon, Dohoon;Kim, Ho;Lee, Inhyung
    • Journal of Veterinary Science
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    • 제23권5호
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    • pp.75.1-75.7
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    • 2022
  • Background: Since 2013, the number of requests for diagnosis for horses based on neurological symptoms has increased rapidly in South Korea. The affected horses have commonly exhibited symptoms of acute seasonal hindlimb ataxia. A previous study from 2015-2016 identified Setaria digitata as the causative agent. Objectives: This study is an epidemiological investigation to find out risk factors related to the rapid increase in hindlimb ataxia of horses due to aberrant parasites in South Korea. Methods: An epidemiological investigation was conducted on 155 cohabiting horses in 41 horse ranches where the disease occurred. The surrounding environment was investigated at the disease-causing horse ranches (n = 41) and 20, randomly selected, non-infected ranches. Results: Hindlimb ataxia was confirmed in nine cohabiting horses; this was presumed to be caused by ectopic parasitism. Environments that mosquitoes inhabit, such as paddy fields within 2 km and less than 0.5 km from a river, had the greatest association with disease occurrence. Conclusions: Most horse ranches in South Korea are situated in favorable environments for mosquitoes. Moreover, the number of mosquitoes in the country has increased since 2013 due to climate change. Additional research is required; however, these data show that it is necessary to establish guidelines for the use of anthelmintic agents based on local factors in South Korea and disinfection of the environment to prevent disease outbreaks.

CBP-Mediated Acetylation of Importin α Mediates Calcium-Dependent Nucleocytoplasmic Transport of Selective Proteins in Drosophila Neurons

  • Cho, Jae Ho;Jo, Min Gu;Kim, Eun Seon;Lee, Na Yoon;Kim, Soon Ha;Chung, Chang Geon;Park, Jeong Hyang;Lee, Sung Bae
    • Molecules and Cells
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    • 제45권11호
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    • pp.855-867
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    • 2022
  • For proper function of proteins, their subcellular localization needs to be monitored and regulated in response to the changes in cellular demands. In this regard, dysregulation in the nucleocytoplasmic transport (NCT) of proteins is closely associated with the pathogenesis of various neurodegenerative diseases. However, it remains unclear whether there exists an intrinsic regulatory pathway(s) that controls NCT of proteins either in a commonly shared manner or in a target-selectively different manner. To dissect between these possibilities, in the current study, we investigated the molecular mechanism regulating NCT of truncated ataxin-3 (ATXN3) proteins of which genetic mutation leads to a type of polyglutamine (polyQ) diseases, in comparison with that of TDP-43. In Drosophila dendritic arborization (da) neurons, we observed dynamic changes in the subcellular localization of truncated ATXN3 proteins between the nucleus and the cytosol during development. Moreover, ectopic neuronal toxicity was induced by truncated ATXN3 proteins upon their nuclear accumulation. Consistent with a previous study showing intracellular calcium-dependent NCT of TDP-43, NCT of ATXN3 was also regulated by intracellular calcium level and involves Importin α3 (Imp α3). Interestingly, NCT of ATXN3, but not TDP-43, was primarily mediated by CBP. We further showed that acetyltransferase activity of CBP is important for NCT of ATXN3, which may acetylate Imp α3 to regulate NCT of ATXN3. These findings demonstrate that CBP-dependent acetylation of Imp α3 is crucial for intracellular calcium-dependent NCT of ATXN3 proteins, different from that of TDP-43, in Drosophila neurons.

RNA Binding Protein Rbms1 Enables Neuronal Differentiation and Radial Migration during Neocortical Development by Binding and Stabilizing the RNA Message for Efr3a

  • Habib, Khadija;Bishayee, Kausik;Kang, Jieun;Sadra, Ali;Huh, Sung-Oh
    • Molecules and Cells
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    • 제45권8호
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    • pp.588-602
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    • 2022
  • Various RNA-binding proteins (RBPs) are key components in RNA metabolism and contribute to several neurodevelopmental disorders. To date, only a few of such RBPs have been characterized for their roles in neocortex development. Here, we show that the RBP, Rbms1, is required for radial migration, polarization and differentiation of neuronal progenitors to neurons in the neocortex development. Rbms1 expression is highest in the early development in the developing cortex, with its expression gradually diminishing from embryonic day 13.5 (E13.5) to postnatal day 0 (P0). From in utero electroporation (IUE) experiments when Rbms1 levels are knocked down in neuronal progenitors, their transition from multipolar to bipolar state is delayed and this is accompanied by a delay in radial migration of these cells. Reduced Rbms1 levels in vivo also reduces differentiation as evidenced by a decrease in levels of several differentiation markers, meanwhile having no significant effects on proliferation and cell cycle rates of these cells. As an RNA binding protein, we profiled the RNA binders of Rbms1 by a cross-linked-RIP sequencing assay, followed by quantitative real-time polymerase chain reaction verification and showed that Rbms1 binds and stabilizes the mRNA for Efr3a, a signaling adapter protein. We also demonstrate that ectopic Efr3a can recover the cells from the migration defects due to loss of Rbms1, both in vivo and in vitro migration assays with cultured cells. These imply that one of the functions of Rbms1 involves the stabilization of Efr3a RNA message, required for migration and maturation of neuronal progenitors in radial migration in the developing neocortex.

Periodontal parameters in orthodontically tractioned teeth: A systematic review and meta-analysis

  • de Mattos, Paola Marques;Goncalves, Flavio Magno;Basso, Isabela Bittencourt;Ferraz, Aline Xavier;Zeigelboim, Bianca Simone;Stechman-Neto, Jose;Santos, Rosane Sampaio;de Araujo, Cristiano Miranda;Guariza-Filho, Odilon
    • 대한치과교정학회지
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    • 제52권6호
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    • pp.420-431
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    • 2022
  • Objective: This systematic review aimed to evaluate periodontal parameters in orthodontically tractioned teeth compared with the respective non-tractioned contralateral teeth. Methods: Search strategies were developed for six electronic databases and gray literature. Random-effects meta-analyses were performed for the outcomes of interest. Furthermore, the certainty of the evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) tool. Results: Overall, 2,082 articles were identified, of which 24 were selected for the qualitative synthesis. A significant difference was observed between the impacted and contralateral teeth (mean difference [MD] = 0.25; 95% confidence interval [CI] = 0.10-0.40; I2 = 0%) when the gingival index was evaluated. Additionally, impacted teeth showed a greater probing depth, with a significant mean difference between the groups (MD = 0.14; 95% CI = 0.07-0.20; I2 = 6%). Most studies had a low risk of bias; however, the certainty of the evidence was very low owing to the design of existing studies. Conclusions: The evidence in the literature indicated that tractioned teeth might show worsening of periodontal parameters related to the gingival index and probing depth; however, the evidence remains uncertain about this outcome. Furthermore, probing depth should be considered regarding its clinical significance because of the small effect size observed.

Mid-term outcomes of bony increased offset-reverse total shoulder arthroplasty in the Asian population

  • Tankshali, Kirtan;Suh, Dong-Whan;Ji, Jong-Hun;Kim, Chang-Yeon
    • Clinics in Shoulder and Elbow
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    • 제24권3호
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    • pp.125-134
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    • 2021
  • Background: To evaluate clinical and radiological outcomes of bony increased offset-reverse total shoulder arthroplasty (BIO-RSA) in the Asian population at mid-term follow-up. Methods: From June 2012 to August 2017 at a single center, 43 patients underwent BIO-RSA, and 38 patients with minimum 2 years follow-up were enrolled. We evaluated the clinical and radiological outcomes, and complications at the last follow-up. In addition, we divided these patients into notching and no-notching groups and compared the demographics, preoperative, and postoperative characteristics of patients. Results: Visual analogue scale, American Shoulder and Elbow Surgeons, University of California-Los Angeles Shoulder Scale, and Simple Shoulder Test scores improved significantly from preoperative (5.00, 3.93, 1.72, 3.94) to postoperative (1.72, 78.91, 28.34, 7.66) (p<0.05) outcomes. All range of motion except internal rotation improved significantly at the final follow-up (p<0.05), and the bone graft was well-incorporated with the native glenoid in all patients (100%). However, scapular notching was observed in 20 of 38 patients (53%). In the comparison between notching and no-notching groups (18 vs. 20 patients), there were no significant differences in demographics, radiological parameters, and clinical outcomes except acromion-greater tuberosity (AT) distance (p=0.003). Intraoperative complications included three metaphyseal fractures and one inferior screw malposition. Postoperative complications included ectopic ossification, scapular neck stress fracture, humeral stem relaxation, and late infection in one case each. Conclusions: BIO-RSA showed improved clinical outcomes at mid-term follow-up in Asian population. However, we observed higher scapular notching compared to the previous studies. In addition, adequate glenoid lateralization with appropriate humeral lengthening (AT distance) might reduce scapular notching.

The CCAAT-box transcription factor, NF-Y complex, mediates the specification of the IL1 neurons in C. elegans

  • Woojung Heo;Hyeonjeong Hwang;Jimin Kim;Seung Hee Oh;Youngseok Yu;Jae-Hyung Lee;Kyuhyung Kim
    • BMB Reports
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    • 제56권3호
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    • pp.153-159
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    • 2023
  • Neuronal differentiation is highly coordinated through a cascade of gene expression, mediated via interactions between trans-acting transcription factors and cis-regulatory elements of their target genes. However, the mechanisms of transcriptional regulation that determine neuronal cell-fate are not fully understood. Here, we show that the nuclear transcription factor Y (NF-Y) subunit, NFYA-1, is necessary and sufficient to express the flp-3 neuropeptide gene in the IL1 neurons of C. elegans. flp-3 expression is decreased in dorsal and lateral, but not ventral IL1s of nfya-1 mutants. The expression of another terminally differentiated gene, eat-4 vesicular glutamate transporter, is abolished, whereas the unc-8 DEG/ENaC gene and pan-neuronal genes are expressed normally in IL1s of nfya-1 mutants. nfya-1 is expressed in and acts in IL1s to regulate flp-3 and eat-4 expression. Ectopic expression of NFYA-1 drives the expression of flp-3 gene in other cell-types. Promoter analysis of IL1-expressed genes results in the identification of several cis-regulatory motifs which are necessary for IL1 expression, including a putative CCAAT-box located in the flp-3 promoter that NFYA-1 directly interacts with. NFYA-1 and NFYA-2, together with NFYB-1 and NFYC-1, exhibit partly or fully redundant roles in the regulation of flp-3 or unc-8 expression, respectively. Taken together, our data indicate that the NF-Y complex regulates neuronal subtype-specification via regulating a set of terminal-differentiation genes.

한의 난임 치료에 활용되는 평가지표와 평가도구 사용 현황 조사 및 고찰 (Review of Indicators and Tools used to Assess Korean Medicine Infertility Treatment)

  • 이수진;김동일;최수지
    • 대한한방부인과학회지
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    • 제36권3호
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    • pp.173-195
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    • 2023
  • Objectives: To investigate and analyze the assessment indicators and tools used in clinical practice to assess Korean medicine (KM) treatment for infertility, and to establish a basis for assessment tools to diagnose and assess infertility. Methods: Relevant studies published until March 2023 were extracted from Pubmed, Research Information Sharing Service, and National Digital Science Library databases. Results: Sixty-four studies comprising 4,105 patients were included. We investigated pregnancy outcomes, and assessed pregnancy- and childbirth-related factors, overall health, reproductive health, and mental health. Pregnancy result was most common primary outcome. Ongoing pregnancy, stillbirth, miscarriage, and ectopic pregnancy rates were suggested as indicators of pregnancy and childbirth-related assessment. Overall health was most commonly assessed with Likert and Visual analogue scale (VAS). Among reproductive health variables, menstrual history was most frequently assessed. Moreover, indicators such as reproductive function, sexual intercourse, and gynecological disease were assessed. The Infertility Stress Scale and the Fertility Quality of Life tool (FertiQoL) were used to assess mental health. Conclusions: Subjective scales and objective assessment tools, such as the Likert scale and blood tests/ultrasonography, respectively, are used to assess KM infertility treatment. Inconsistent assessment tools make quantitative analyses more challenging. The development of a standardized mental and physical function assessment questionnaire with confirmed reliability and validity ensure the effectiveness of KM infertility treatment, and promote future studies on infertility treatment.