Generation of disease-specific induced pluripotent stem cells from patients with rheumatoid arthritis and osteoarthritis

Lee, Jaecheol,Kim, Youngkyun,Yi, Hyoju,Diecke, Sebastian,Kim, Juryun,Jung, Hyerin,Rim, Yeri Alice,Jung, Seung Min,Kim, Myungshin,Kim, Yong Goo,Park, Sung-Hwan,Kim, Ho-Youn,Ju, Ji Hyeon BioMed Central 2014 ARTHRITIS RESEARCH AND THERAPY Vol.16 No.1

<P><B>Introduction</B></P><P>Since the concept of reprogramming mature somatic cells to generate induced pluripotent stem cells (iPSCs) was demonstrated in 2006, iPSCs have become a potential substitute for embryonic stem cells (ESCs) given their pluripotency and “stemness” characteristics, which resemble those of ESCs. We investigated to reprogram fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) to generate iPSCs using a 4-in-1 lentiviral vector system.</P><P><B>Methods</B></P><P>A 4-in-1 lentiviral vector containing Oct4, Sox2, Klf4, and c-Myc was transduced into RA and OA FLSs isolated from the synovia of two RA patients and two OA patients. Immunohistochemical staining and real-time PCR studies were performed to demonstrate the pluripotency of iPSCs. Chromosomal abnormalities were determined based on the karyotype. SCID-beige mice were injected with iPSCs and sacrificed to test for teratoma formation.</P><P><B>Results</B></P><P>After 14 days of transduction using the 4-in-1 lentiviral vector, RA FLSs and OA FLSs were transformed into spherical shapes that resembled embryonic stem cell colonies. Colonies were picked and cultivated on matrigel plates to produce iPSC lines. Real-time PCR of RA and OA iPSCs detected positive markers of pluripotency. Immunohistochemical staining tests with Nanog, Oct4, Sox2, Tra-1-80, Tra-1-60, and SSEA-4 were also positive. Teratomas that comprised three compartments of ectoderm, mesoderm, and endoderm were formed at the injection sites of iPSCs. Established iPSCs were shown to be compatible by karyotyping. Finally, we confirmed that the patient-derived iPSCs were able to differentiate into osteoblast, which was shown by an osteoimage mineralization assay.</P><P><B>Conclusion</B></P><P>FLSs derived from RA and OA could be cell resources for iPSC reprogramming. Disease- and patient-specific iPSCs have the potential to be applied in clinical settings as source materials for molecular diagnosis and regenerative therapy.</P>

Design and Analysis of a Low-cost Approximate Adder with OR and Zero Truncation

Hyoju Seo,Jungwon Lee,Donghui Lee,Beomjun Kim,Yongtae Kim 대한전자공학회 2021 IEIE Transactions on Smart Processing & Computing Vol.10 No.4

This paper proposes a new cost-effective approximate adder that exploits OR operation and zero truncation. The proposed approximation technique reduces the hardware cost significantly while maintaining comparable computation accuracy. The proposed adder achieved 48%, 51%, and 48% reductions in the area, delay, and power, respectively, compared to a traditional adder when implemented in 32-nm CMOS technology. The proposed design could also enhance the normalized mean error distance up to 29% compare to the approximate adders considered in this paper. The adder showed an excellent tradeoff performance between the hardware and computation accuracy. Furthermore, the proposed adder was adopted in a digital image processing application, and the benefit of the proposed adder is demonstrated.

Contextual distribution of English loanword word-initial tensification in Korean

Hyoju Kim 한국음운론학회 2016 음성·음운·형태론 연구 Vol.22 No.2

This study investigates the contextual distribution of word-initial tensification of English loanwords in Korean. In English loanwords, word-initial lax stops are optionally tensified. Based on two different data sources, it is confirmed that word-initial tensification of English loanwords shows three statistically significant contextual effects, which are referred to as height, length, and assimilation effect, respectively. The present study found that the word-initial tensification of English loanwords is significantly more likely to occur when the height of the vowel following the tensification site is non-high compared to high, when the word is monosyllabic rather than multisyllabic, and when the onset of the syllable following the tensification site is a tense /s’/. In order to explore the underlying reason for each contextual effect, two possible sources were investigated. The first one was the word-initial tensification of native Korean words that shows optional tensification like loanwords. The second one was the native Korean lexicon. Given the claims that the variable patterns of loanwords may reflect covert statistical generalizations of the native lexicon (Kubozono 2006, Zuraw 2010), the tendencies found in loanwords may also reflect statistical trends displayed by the Korean lexicon. The survey demonstrates that the phonological distribution of loanword tensification partially reflects the contextual distribution of both native tensification and the lexicon. In addition, acoustic and articulatory phonetic accounts are proposed with respect to the contextual effects. Finally, a learning simulation for the observed trends is conducted with a constraint set, adopting the concept of the Maximum Entropy model. The results show that the proper constraints and weights accurately predict the distribution observed in English loanwords.

Position and Frequency Control of Strain-Induced Quantum Emitters in WSe₂ Monolayers

Kim, Hyoju,Moon, Jong Sung,Noh, Gichang,Lee, Jieun,Kim, Je-Hyung American Chemical Society 2019 Nano letters Vol.19 No.10

<P>Future scalable and integrated quantum photonic systems require deterministic generation and control of multiple quantum emitters. Although various approaches for spatial and spectral control of the quantum emitters have been developed, on-chip control of both position and frequency is still a long-standing goal in solid-state quantum emitters. Here, we demonstrate simultaneous control of position and frequency of the quantum emitters from transition metal dichalcogenide monolayers. Atomically thin two-dimensional materials are inherently sensitive to external strain and offer a new opportunity of creating and controlling the quantum emitters by engineering strain. We fabricate an electrostatically actuated microcantilever with nanopyramid patterns, providing a local strain engineering platform for the WSe<SUB>2</SUB> monolayer. The integrated WSe<SUB>2</SUB> generates high-purity single photon emission at patterned positions with a tuning range up to 3.5 meV. Together with the position and frequency control, we investigate the strain response on the fine-structure splitting and confirm 11% reduction in the fine splitting at the estimated tensile strain of 0.07%.</P> [FIG OMISSION]</BR>

Cell-penetratingandenzyme-stabilizing properties of α-helix domain of 30Kc19 protein

Hyoju KIM,Jina RYU,Hee Ho PARK,Hong Jai LEE,Tai Hyun PARK 한국생물공학회 2014 한국생물공학회 학술대회 Vol.2014 No.10

Effect of acellular dermal matrix as a delivery carrier of adipose‐derived mesenchymal stem cells on bone regeneration

Kim, Hee Jung,Park, Sung Su,Oh, Sun Young,Kim, Hyoju,Kweon, Oh‐,Kyeong,Woo, Heung Myong,Kim, Wan Hee Wiley Subscription Services, Inc., A Wiley Company 2012 JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B Vol.b100 No.6

<P><B>Abstract</B></P><P>The purpose of this study is to evaluate the effect of acellular dermal matrix (ADM) as a delivery carrier of adipose‐derived mesenchymal stem cells (ASCs) on bone regeneration in athymic murine calvarial bone defect. Paired‐critical size defects in nude rat skull were made. The right‐side defects received ASCs/ADM or only ADM, whereas the left‐side defect was not treated. In 3D images, new bone formation in the ASCs/ADM group was apparent at 4 wk, but in the ADM group at 8 wk. At 4 and 8 wk, bone mineral density and tissue volume in rats that received ASCs/ADM were significantly greater than rats that received ADM and control groups. Histological examination revealed that the defect was repaired by bone in the ASCs/ADM group, whereas only minimal bone island with fibrous connection was observed in the control group. In histomorphometric analysis, the total healing score in the ASCs/ADM group at 4 wk was significantly higher than the ADM and negative control group, whereas the score of 8 wk was similar between the ASCs/ADM and ADM group. ASCs/ADM implants promote new bone formation more rapidly than ADM only or no treatment. ADM seeded with ASCs may be potentially useful as a future biomaterial option in bone implants. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 1645–1653, 2012.</P>

Preliminary study of presumptive intradural-intramedullary intervertebral disc extrusion in 20 dogs

Kim, Jaehwan,Kim, Hyoju,Hwang, Jeongyeon,Eom, Kidong The Korean Society of Veterinary Science 2020 Journal of Veterinary Science Vol.21 No.2

Background: Intradural-intramedullary intervertebral disc extrusion (IIVDE) is a rare condition of intervertebral disc disease. However, the diagnosis of IIVDE is challenging because the prognosis and imaging characteristics are poorly characterized. Objectives: We aimed to describe the clinical and imaging characteristics of tentatively diagnosed IIVDE in dogs to assess the prognostic utility of neurological grade and magnetic resonance imaging (MRI) findings. Methods: Twenty dogs were included in this retrospective cohort study. Results: Nonchondrodystrophic breeds (n = 16) were more predisposed than chondrodystrophic breeds. Most dogs showed acute onset of clinical signs. Neurological examination at admission showed predominant non-ambulatory paraparesis (n = 9); paresis (n = 16) was confirmed more frequently than paralysis (n = 4). Follow-up neurological examination results were only available for 11 dogs, ten of whom showed neurological improvement and 8 showed successful outcomes at 1 month. The characteristic MRI findings include thoracic vertebra (T)2 hyperintense, T1 hypointense, intramedullary linear tracts with reduced disc volume, and cleft of the annulus fibrosus. None of the MRI measurements were significantly correlated with neurological grade at admission. Neurological grade did not differ according to the presence of parenchymal hemorrhage, parenchymal contrast enhancement, and meningeal contrast enhancement. Neurological grades at admission showed a statistical correlation with those observed at the 1-month follow-up (r = 0.814, p = 0.02). Conclusions: IIVDE is a rare form of disc extrusion commonly experienced after physical activity or trauma and most frequently affects the cranial-cervical and thoracolumbar regions of nonchondrodystrophic dog breeds. Neurological score at admission emerged as a more useful prognostic indicator than MRI findings in dogs with suspected IIVDE.

Far lateral lumbar disc extrusion in a dachshund dog

Kim, Jaehwan,Kim, Hyoju,Hwang, Jeongyeon,Eom, Kidong The Korean Society of Veterinary Science 2019 大韓獸醫學會誌 Vol.59 No.3

A 6-year-old Dachshund was presented with acute, non-localized pain without neurological dysfunction. Radiography revealed multiple calcifications of intervertebral discs and narrowing of disc space in the thoracolumbar region. Computed tomography and magnetic resonance imaging revealed calcified disc-like material entrapped in the left extraforaminal area and showed a displaced nerve root. Fenestration and removal of the extruded disc material were performed in a routine manner. Histopathological examination showed degenerative disc materials with severe calcification both in the nucleus pulposus and around the annulus fibrosis. Based on imaging, surgical, and histopathologic results, the dog was diagnosed with far lateral lumbar disc extrusion.

Preliminary study of presumptive intradural-intramedullary intervertebral disc extrusion in 20 dogs

Jaehwan Kim,Hyoju Kim,Jeongyeon Hwang,Kidong Eom 대한수의학회 2020 Journal of Veterinary Science Vol.21 No.4

Background: Intradural-intramedullary intervertebral disc extrusion (IIVDE) is a rare condition of intervertebral disc disease. However, the diagnosis of IIVDE is challenging because the prognosis and imaging characteristics are poorly characterized. Objectives: We aimed to describe the clinical and imaging characteristics of tentatively diagnosed IIVDE in dogs to assess the prognostic utility of neurological grade and MRI findings. Methods: Twenty dogs were included in this retrospective cohort study. Results: Nonchondrodystrophic breeds (n=16) were more predisposed than chondrodystrophic breeds. Most dogs showed acute onset of clinical signs. Neurological examination at admission showed predominant non-ambulatory paraparesis (n=9); paresis (n=16) was confirmed more frequently than paralysis (n=4). Follow-up neurological examination results were only available for 11 dogs, ten of whom showed neurological improvement and eight showed successful outcomes at 1 month. The characteristic MRI findings include T2 hyperintense, T1 hypointense, intramedullary linear tracts with reduced disc volume, and cleft of the annulus fibrosus. None of the MRI measurements were significantly correlated with neurological grade at admission. Neurological grade did not differ according to the presence of parenchymal hemorrhage, parenchymal contrast enhancement, and meningeal contrast enhancement. Neurological grades at admission showed a statistical correlation with those observed at the 1-month follow-up (r=0.814, P=0.02). Conclusions: IIVDE is a rare form of disc extrusion commonly experienced after physical activity or trauma and most frequently affects the cranial-cervical and thoracolumbar regions of nonchondrodystrophic dog breeds. Neurological score at admission emerged as a more useful prognostic indicator than MRI findings in dogs with suspected IIVDE.

Induced production of anti-etanercept antibody in collagen-induced arthritis

YI, HYOJU,KIM, JURYUN,JUNG, HYERIN,RIM, YERI ALICE,KIM, YOUNGKYUN,JUNG, SEUNG MIN,PARK, SUNG-HWAN,JU, JI HYEON Spandidos Publications 2014 MOLECULAR MEDICINE REPORTS Vol.9 No.6

<P>Etanercept is a widespread biological drug for the treatment of rheumatoid arthritis, which inhibits tumor necrosis factor-α (TNF-α). Recently, the presence of antibodies targeting TNF-α inhibitors such as infliximab and adalimumab, was reported. However, few reports have studied etanercept in a mouse model of arthritis. We investigated the induction of anti-etanercept antibody production, along with the antibody's potential interfering effects on the biological function of etanercept, in mice with collagen-induced arthritis (CIA). CIA mice received an intraperitoneal injection of etanercept (25, 100 or 400 ?g per mouse). The degree of inflammation and cartilage erosion was evaluated, and the number of osteoclasts in the ankle joints was assessed by TRAP staining. The level of pro-inflammatory cytokines in the serum was measured. To analyze the anti-osteoporotic effect of etanercept, microfocal computed tomography analyses of femurs and tibias were performed. Etanercept treatment decreased both the incidence and severity of arthritis in a dose-dependent manner, except for the highest dose of 400 ?g. The mice that were treated with 25 and 100 ?g etanercept showed an improvement in inflammation, cartilage damage, and even bone loss. However, mice treated with 400 ?g etanercept showed no significant improvement in any of the tested parameters. Using a customized enzyme-linked immunosorbent assay (ELISA), the presence of the anti-etanercept antibody was detected in the serum in this treatment-refractory group. The therapeutic effect of etanercept was reduced in the CIA mice that developed the anti-etanercept antibody. In conclusion, the production of an anti-etanercept antibody can be induced in CIA mice, and this antibody can considerably reduce the anti-arthritic and anti-osteoporotic effects of etanercept.</P>