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Quantification and visualization of metastatic lung tumors in mice
Lee Ha Neul,Kim Seyl,Park Sooah,Jung Woonggyu,Kang Jin Seok 한국독성학회 2022 Toxicological Research Vol.38 No.4
Histopathological examination is important for the diagnosis of various diseases. Conventional histopathology provides a two-dimensional view of the tissues, and requires the tissue to be extracted, fixed, and processed using histotechnology techniques. However, there is an increasing need for three-dimensional (3D) images of structures in biomedical research. The objective of this study was to develop reliable, objective tools for visualizing and quantifying metastatic tumors in mouse lung using micro-computed tomography (micro-CT), optical coherence tomography (OCT), and field emission-scanning electron microscopy (FE-SEM). Melanoma cells were intravenously injected into the tail vein of 8-week-old C57BL/6 mice. The mice were euthanized at 2 or 4 weeks after injection. Lungs were fixed and examined by micro-CT, OCT, FE-SEM, and histopathological observation. Micro-CT clearly distinguished between tumor and normal cells in surface and deep lesions, thereby allowing 3D quantification of the tumor volume. OCT showed a clear difference between the tumor and surrounding normal tissues. FE-SEM clearly showed round tumor cells, mainly located in the alveolar wall and growing inside the alveoli. Therefore, whole-tumor 3D imaging successfully visualized the metastatic tumor and quantified its volume. This promising approach will allow for fast and label-free 3D phenotyping of diverse tissue structures.
Familial Otosclerosis Associated with Osteogenesis Imperfecta: A Case Report
Lee Ha Neul,Jeon Hyun Jong,서영준 대한청각학회 2021 Journal of Audiology & Otology Vol.25 No.4
Otosclerosis, a hereditary disorder characterized by disordered resorption and deposition of bone, results in progressive hearing loss. Osteogenesis imperfecta (OI) is a genetic disorder characterized by recurrent fractures, blue sclera, and varying degrees of hearing impairment; and is a known risk factor for otosclerosis. After adolescence, the risk of fracture decreases, reducing the need for follow-up in OI. However, otosclerosis is a progressive disorder. In this report, we discuss two cases of familial otosclerosis with different clinical features. We hypothesize that the difference in hearing level correlates with the difference in computed tomography findings. The mother, whose case was considered severe, was prescribed hearing aids, while the daughter, who had normal hearing level, was regularly followed up.
Endothelial miR-26a regulates VEGF-Nogo-B receptor-mediated angiogenesis
( Ha-neul Jo ),( Hyesoo Kang ),( Aram Lee ),( Jihea Choi ),( Woochul Chang ),( Myeong-sok Lee ),( Jongmin Kim ) 생화학분자생물학회 2017 BMB Reports Vol.50 No.7
The Nogo-B receptor (NgBR) is necessary for not only Nogo-B-mediated angiogenesis but also vascular endothelial growth factor (VEGF) -induced angiogenesis. However, the molecular mechanisms underlying the regulatory role of the VEGF-NgBR axis in angiogenesis are not fully understood. Here, we report that miR-26a serves as a critical regulator of VEGF-mediated angiogenesis through directly targeting NgBR in endothelial cells (ECs). Stimulation of ECs by VEGF increased the expression of NgBR and decreased the expression of miR-26a. In addition, miR-26a decreased the VEGF-induced migration and proliferation of ECs. Moreover, miR-26a overexpression in ECs decreased the VEGF-induced phosphorylation of the endothelial nitric oxide synthase (eNOS) and the production of nitric oxide, which is important for angiogenesis. Overall, these data suggest that miR-26a plays a key role in VEGF-mediated angiogenesis through the modulation of eNOS activity, which is mediated by its ability to regulate NgBR expression by directly targeting the NgBR 3`-UTR. [BMB Reports 2017; 50(7): 384-389]
Novel Embryoid Body-Based Method to Derive Mesenchymal Stem Cells from Human Embryonic Stem Cells
Lee, Eun Ju,Lee, Ha-Neul,Kang, Hyun-Jae,Kim, Keum-Hyun,Hur, Jin,Cho, Hyun-Jai,Lee, Jaewon,Chung, Hyung-Min,Cho, Jaejin,Cho, Mee-Young,Oh, Sun-Kyung,Moon, Shin-Yong,Park, Young-Bae,Kim, Hyo-Soo Mary Ann Liebert 2010 Tissue engineering. Part A Vol.16 No.2
<P>Application of human embryonic stem cells (hESCs) to stem-cell therapy is not feasible because of the risk of tumorigenicity and rejection. In contrast, human mesenchymal stem cells (hMSCs) are free from the risk of tumorigenicity and also have immune privilege. However, hMSCs obtained from adults have infinite variety in terms of the biological characteristics and functionality. We report here a new derivation method of hMSCs from hESCs. The derivation of hMSCs from three different hESC lines (SNUhES3, CHA3-hESC, and H9) was performed by embryoid bodies formation and subsequent culture with stage-different media without using inductive xenogenic feeder and mechanical selection procedure. The derived cells were morphologically similar to the unique fingerprint-like pattern of hMSCs and grew stably for at least 35 passages in vitro. These cells had hMSCs-like immunophenotypes: negative for CD34 and CD45; positive for CD29, CD44, CD73, CD90, and CD105. They could be differentiated into multiple lineages including osteocytes, chondrocytes, adipocytes, and myocytes. They maintained normal karyotype during the long-term cultivation and did not show tumorigenicity when transplanted into the immunodeficient mice. In conclusion, the new embryoid body-based derivation method of hMSCs from hESCs is simple, safe, and reproducible in three different hESC lines. We expect that this method will provide a more effective and powerful tool to derive hMSCs from various hESC lines.</P>
Characteristics of late-onset epilepsy and EEG findings in children with autism spectrum disorders
Lee, Ha-Neul,Kang, Hoon-Chul,Kim, Seung-Woo,Kim, Young-Key,Chung, Hee-Jung The Korean Pediatric Society 2011 Clinical and Experimental Pediatrics (CEP) Vol.54 No.1
Purpose: To investigate the clinical characteristics of late-onset epilepsy combined with autism spectrum disorder (ASD), and the relationship between certain types of electroencephalography (EEG) abnormalities in ASD and associated neuropsychological problems. Methods: Thirty patients diagnosed with ASD in early childhood and later developed clinical seizures were reviewed retrospectively. First, the clinical characteristics, language and behavioral regression, and EEG findings of these late-onset epilepsy patients with ASD were investigated. The patients were then classified into 2 groups according to the severity of the EEG abnormalities in the background rhythm and paroxysmal discharges. In the severe group, EEG showed persistent asymmetry, slow and disorganized background rhythms, and continuous sharp and slow waves during slow sleep (CSWS). Results: Between the two groups, there was no statistically significant difference in mean age (P=0.259), age of epilepsy diagnosis (P=0.237), associated family history (P=0.074), and positive abnormal magnetic resonance image (MRI) findings (P=0.084). The severe EEG group tended to have more neuropsychological problems (P=0.074). The severe group statistically showed more electrographic seizures in EEG (P=0.000). Rett syndrome was correlated with more severe EEG abnormalities (P=0.002). Although formal cognitive function tests were not performed, the parents reported an improvement in neuropsychological function on the follow up checkup according to a parent's questionnaire. Conclusion: Although some ASD patients with late-onset epilepsy showed severe EEG abnormalities, including CSWS, they generally showed an improvement in EEG and clinical symptoms in the longterm follow up. In addition, severe EEG abnormalities tended to be related to the neuropsychological function.
Integrated diagnostic approach of pediatric neuromuscular disorders
Lee, Ha Neul,Lee, Young-Mock Korean Society of Medical Genetics and Genomics 2018 대한의학유전학회지 Vol.15 No.2
Clinical and genetic heterogeneity in association with overlapping spectrum is characteristic in pediatric neuromuscular disorders, which makes confirmative diagnosis difficult and time consuming. Considering evolution of molecular genetic diagnosis and resultant upcoming genetically modifiable therapeutic options, rapid and cost-effective genetic testing should be applied in conjunction with existing diagnostic methods of clinical examinations, laboratory tests, electrophysiologic studies and pathologic studies. Earlier correct diagnosis would enable better clinical management for these patients in addition to new genetic drug options and genetic counseling.
Lee, Mee-Ryung,Choi, Ha-Neul,Ha, Ho-Kyung,Lee, Won-Jae Korean Society for Food Science of Animal Resource 2013 한국축산식품학회지 Vol.33 No.1
The aims of this research were to produce oil-in-water ${\beta}$-lactoglobulin/alginate (${\beta}$-lg/Al) nanoemulsions loaded with coenzyme $Q_{10}$ and to investigate the combined effects of heating temperature and alginate concentration on the physicochemical properties and encapsulation efficiency of ${\beta}$-lg/Al nanoemulsions. In ${\beta}$-lg/Al nanoemulsions production, various heating temperatures (60, 65, and $70^{\circ}C$) and alginate concentrations (0, 0.01, 0.03, and 0.05%) were used. A transmission electron microscopy was used to observe morphologies of ${\beta}$-lg/Al nanoemulsions. Droplet size and zeta-potential values of ${\beta}$-lg/Al nanoemulsions and encapsulation efficiency of coenzyme $Q_{10}$ were determined by electrophoretic light scattering spectrophotometer and HPLC, respectively. The spherically shaped ${\beta}$-lg/Al nanoemulsions with the size of 169 to 220 nm were successfully formed. The heat treatments from 60 to $70^{\circ}C$ resulted in a significant (p<0.05) increase in droplet size, polydispersity, zeta-potential value of ${\beta}$-lg/Al nanoemulsions, and encapsulation efficiency of coenzyme $Q_{10}$. As alginate concentration was increased from 0 to 0.05%, there was an increase in the polydispersity index of ${\beta}$-lg/Al nanoemulsions and encapsulation efficiency of coenzyme $Q_{10}$. This study demonstrates that heating temperature and alginate concentration had a major impact on the size, polydispersity, zeta-potential value and encapsulation efficiency of coenzyme $Q_{10}$ in ${\beta}$-lg/Al nanoemulsions.