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Korean Red Ginseng attenuates Di-(2-ethylhexyl) phthalate-induced inflammatory response in endometrial cancer cells and an endometriosis mouse model

  • Song, Heewon;Won, Ji Eun;Lee, Jeonggeun;Han, Hee Dong;Lee, YoungJoo
    • Journal of Ginseng Research
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    • v.46 no.4
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    • pp.592-600
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    • 2022
  • Background: Di-(2-ethylhexyl) phthalate (DEHP) is the most common endocrine disrupting chemical used as a plasticizer. DEHP is associated with the development of endometrium-related diseases through the induction of inflammation. The major therapeutic approaches against endometrial cancer and endometriosis involve the suppression of inflammatory response. Korean Red Ginseng (KRG) is a natural product with anti-inflammatory and anti-carcinogenic properties. Thus, the purpose of this study is to investigate the effects of KRG on DEHP-induced inflammatory response in endometrial cancer Ishikawa cells and a mouse model of endometriosis. Methods: RNA-sequencing was performed and analyzed on DEHP-treated Ishikawa cells in the presence and absence of KRG. The effects of KRG on DEHP-induced cyclooxygenase-2 (COX-2) mRNA levels in Ishikawa cells were determined by RT-qPCR. Furthermore, the effects of KRG on the extracellular signal-regulated kinases (ERKs) pathway, COX-2, and nuclear factor-kappa B (NF-kB) p65 after DEHP treatment of Ishikawa cells were evaluated by western blotting. In the mouse model, the severity of endometriosis induced by DEHP and changes in immunohistochemistry were used to assess the protective effect of KRG. Results: According to the RNA-sequencing data, DEHP-induced inflammatory response-related gene expression was downregulated by KRG. Moreover, KRG significantly inhibited DEHP-induced ERK1/2/NF-κB/COX-2 levels in Ishikawa cells. In the mouse model, KRG administration significantly inhibited ectopic endometriosis growth after DEHP-induced endometriosis. Conclusions: Overall, these results suggest that KRG may be a promising lead for the treatment of endometrial cancer and endometriosis via suppression of the inflammatory response.

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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    • v.55 no.2
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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.

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

  • Chaehyun, Na;Hana, Lee;Hansung, Kim;Jihun, Kim
    • Journal of the korean academy of Pediatric Dentistry
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    • v.49 no.3
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    • pp.348-356
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    • 2022
  • Supernumerary teeth develop from excessive proliferation and development of the dental lamina. Supernumerary teeth can cause several problems, including ectopic eruption, delayed eruption, root resorption of adjacent teeth, and diastema. Supernumerary teeth in infancy are rare and have rarely been reported. Case of a 2-day-old infant with 3 supernumerary teeth is presented here and the patient was followed up for 21 months. The erupted supernumerary tooth in the primary dentition was extracted under moderate sedation at the age of 14 months. Microcomputed tomography analysis of the extracted tooth confirmed microscopic root malformation. After extraction, the midline diastema was reduced and oral hygiene improved. Early diagnosis and prompt treatment can prevent complications of supernumerary teeth.

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

  • Jonghwa, Lim;Gimin, Kim;Jaesik, Lee;Soonhyeun, Nam;Hyunjung, Kim
    • Journal of the korean academy of Pediatric Dentistry
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    • v.49 no.2
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    • pp.234-240
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    • 2022
  • Floating-Harbor syndrome (FHS) is a rare genetic disorder. This report introduced in a patient with FHS. Distinctive facial characteristics, severe skeletal class 3 malocclusion with underdeveloped maxilla and protruded mandible, congenital missing teeth, microdontia and ectopic positions of maxillary teeth were presented in the patient. In his twin sister, mild skeletal class 3 malocclusion with protruded mandible was observed but congenital missing teeth and microdontia were not observed. High-arched palate, narrow V-shaped maxillary arch compared to wide and ovoid mandibular arch and inverse relationship between the maxillary and mandibular intermolar width resulted in posterior crossbite were confirmed by model analysis of the patient. These were not observed in the twins. Behaviorally, poor cooperation during dental treatment because of mental retardation was observed in the patient.

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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    • v.23 no.5
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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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    • v.45 no.11
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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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    • v.45 no.8
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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
    • The korean journal of orthodontics
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    • v.52 no.6
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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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    • v.24 no.3
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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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    • v.56 no.3
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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.