• Biomolecules & Therapeutics
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• 제28권5호
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• pp.423-430
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• 2020

Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α-induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α. Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.

• International Journal of Stem Cells
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• 제16권1호
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• pp.93-107
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• 2023

Background and Objectives: Chronic periodontitis can lead to alveolar bone resorption and eventually tooth loss. Stem cells from exfoliated deciduous teeth (SHED) are appropriate bone regeneration seed cells. To track the survival, migration, and differentiation of the transplanted SHED, we used super paramagnetic iron oxide particles (SPIO) Molday ION Rhodamine-B (MIRB) to label and monitor the transplanted cells while repairing periodontal bone defects. Methods and Results: We determined an appropriate dose of MIRB for labeling SHED by examining the growth and osteogenic differentiation of labeled SHED. Finally, SHED was labeled with 25 ㎍ Fe/ml MIRB before being transplanted into rats. Magnetic resonance imaging was used to track SHED survival and migration in vivo due to a low-intensity signal artifact caused by MIRB. HE and immunohistochemical analyses revealed that both MIRB-labeled and unlabeled SHED could promote periodontal bone regeneration. The colocalization of hNUC and MIRB demonstrated that SHED transplanted into rats could survive in vivo. Furthermore, some MIRB-positive cells expressed the osteoblast and osteocyte markers OCN and DMP1, respectively. Enzyme-linked immunosorbent assay revealed that SHED could secrete protein factors, such as IGF-1, OCN, ALP, IL-4, VEGF, and bFGF, which promote bone regeneration. Immunofluorescence staining revealed that the transplanted SHED was surrounded by a large number of host-derived Runx2- and Col II-positive cells that played important roles in the bone healing process. Conclusions: SHED could promote periodontal bone regeneration in rats, and the survival of SHED could be tracked in vivo by labeling them with MIRB. SHED are likely to promote bone healing through both direct differentiation and paracrine mechanisms.

• Parasites, Hosts and Diseases
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• 제60권2호
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• pp.127-131
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• 2022

Feline hemotropic mycoplasmosis (hemoplasmosis) is an infection of the red blood cells caused by the Mycoplasma haemofelis (Mhf), Candidatus Mycoplasma haemominutum (CMhm), and Candidatus Mycoplasma turicensis (CMt). The existence of Mhf, CMhm, and CMt has been demonstrated in feral cats in Korea using molecular methods, but no clinical cases have yet been reported. This study reports 2 clinical cases of hemotropic mycoplasmosis caused by CMhm and CMt in 2 anemic cats. The first case was a client-owned intact female domestic shorthair cat that presented with fever, pale mucous membranes, and normocytic normochromic non-regenerative anemia. Prior to referral, an immunosuppressive prednisolone dose was administered at the local veterinary clinic for 1 month. The cat was diagnosed with high-grade alimentary lymphoma. Organisms were found on the surface of the red blood cells on blood smear examination. The second case was of a rescued cat that presented with dehydration and fever. The cat had normocytic normochromic non-regenerative anemia. Necropsy revealed concurrent feline infectious peritonitis. Polymerase chain reaction assay targeting 16S rRNA revealed CMhm infection in case 1 and dual infection of CMhm and CMt in case 2. Normocytic normochromic non-regenerative anemia was observed in both cats before and during the management of the systemic inflammation. This is the first clinical case report in Korea to demonstrate CMhm and CMt infections in symptomatic cats.

• 한국재료학회지
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• 제24권12호
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• pp.704-709
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• 2014

In this study, we fabricated a novel micro porous hybrid scaffold of biphasic calcium phosphate (BCP) and a polylectrolyte complex (PEC) of chitosan (CS) and hyaluronic acid (HA). The fabrication process included loading of CS-HA PEC in a bare BCP scaffold followed by lypophilization. SEM observation and porosimetry revealed that the scaffold was full of micro and macro pores with total porosity of more than 60 % and pore size in the range of $20{\sim}200{\mu}m$. The composite scaffold was mechanically stronger than the bare BCP scaffold and was significantly stronger than the CS-HA PEC polymer scaffold. Bone morphogenetic growth factor (BMP-2) was immobilized in CS-HA PEC in order to integrate the osteoinductive potentiality required for osteogenesis. The BCP frame, prepared by sponge replica, worked as a physical barrier that prolonged the BMP-2 release significantly. The preliminary biocompatibility data show improved biological performance of the BMP-2 immobilized hybrid scaffold in the presence of rabbit bone marrow stem cells (rBMSC).

• 한국진공학회지
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• 제16권1호
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• pp.58-64
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• 2007

조직공학재생의학(조재학)은 생명과학과공학의 기본개념을 응용하여 생체조직을 만들고, 복원시키고, 변형시키기 위하여 새로운 디바이스나 생체조직 대용품을 만드는 학문분야이다. 조재학은 다학제간 연구개발하는 분야로써 매우 혁신적인 건강관리 및 치료 학문분야이다. 조재학의 큰 특징은 발전 속도가 빠른 첨단 과학 기술을 바탕으로 하고 있기 때문에 발전 속도가 빠르다는 점과 여러 분야의 지식과 기술을 함께 이용하기 때문에 다른 학문보다 관련 분야에 대하여 더욱 더 폭 넓은 이해를 필요로 하게 되므로 서로 다른 분야의 지식을 가진 과학자들의 협동 연구가 요구된다. 본 총설에서는 현재의 연구개발 동향 및 결과와 미래 가능성의 이해를 돕기위해 고찰하였다.

• BMB Reports
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• 제47권5호
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• pp.249-255
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• 2014

Polo-like kinase-1 (Plk1) belongs to a family of serine-threonine kinases and plays a critical role in mitotic progression. Plk1 involves in the initiation of mitosis, centrosome maturation, bipolar spindle formation, and cytokinesis, well-reported as traditional functions of Plk1. In this review, we discuss the role of Plk1 during DNA damage response beyond the functions in mitotsis. When DNA is damaged in cells under various stress conditions, the checkpoint mechanism is activated to allow cells to have enough time for repair. When damage is repaired, cells progress continuously their division, which is called checkpoint recovery. If damage is too severe to repair, cells undergo apoptotic pathway. If damage is not completely repaired, cells undergo a process called checkpoint adaptation, and resume cell division cycle with damaged DNA. Plk1 targets and regulates many key factors in the process of damage response, and we deal with these subjects in this review.

• Journal of Pharmaceutical Investigation
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• 제40권6호
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• pp.333-337
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• 2010

Combining cell- and gene-based therapy is a promising therapeutic strategy in regenerative medicine. The aim of this study was to develop genetically modified mesenchymal stem cell (MSC) aggregates using a poly(ethylene glycol) (PEG) hydrogel micro-well array technique. Stable PEG hydrogel micro-well arrays with diameters of 200 to $500\;{\mu}m$ were fabricated and used to generate genetically engineered MSC aggregates. Rat bone marrow-derived MSCs were transfected with a green fluorescent protein (GFP) plasmid as a reporter gene, and aggregated by culturing in the PEG hydrogel micro-well arrays. The resultant cell aggregates had a mean diameter of less than $200\;{\mu}m$, and maintained the mesenchymal phenotype even after genetic modification and cell aggregation. Transplantation of MSC aggregates that are genetically modified to express therapeutic or cell-survival genes may be a potential therapeutic approach for regenerative medicine.

• Genomics & Informatics
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• 제11권4호
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• pp.272-276
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• 2013

Sequence analysis of the 16S rRNA gene has been widely used for the classification of microorganisms. However, we have been unable to clearly identify five Flavobacterium species isolated from a freshwater by using the gene as a single marker, because the evolutionary history is incomplete and the pace of DNA substitutions is relatively rapid in the bacteria. In this study, we tried to classify Flavobacterium species through multilocus sequence analysis (MLSA), which is a practical and reliable technique for the identification or classification of bacteria. The five Flavobacterium species isolated from freshwater and 37 other strains were classified based on six housekeeping genes: gyrB, dnaK, tuf, murG, atpA, and glyA. The genes were amplified by PCR and subjected to DNA sequencing. Based on the combined DNA sequence (4,412 bp) of the six housekeeping genes, we analyzed the phylogenetic relationship among the Flavobacterium species. The results indicated that MLSA, based on the six housekeeping genes, is a trustworthy method for the identification of closely related Flavobacterium species.

• 한국수정란이식학회지
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• 제31권1호
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• pp.9-12
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• 2016

Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-specific growth factors that regulate many critical processes involved in early folliculogenesis and oocyte maturation. In this study, effects of GDF9 and BMP15 treatment during in vitro maturation of porcine oocytes upon development after parthenogenetic activation were investigated. Neither GDF, BMP15 alone nor in combination affects the number and viability of cumulus cells or the rates of oocyte maturation and blastocyst development. However, the treatment of GDF9 on porcine oocytes increased the number of trophectodermal (TE) cells of blastocysts derived from activated oocytes (P<0.05). The treatment of BMP15 increased the cell numbers of both inner cell mass (ICM) and TE cells (P<0.05). The treatment with the combination of GDF9 and BMP15 further increased the numbers of ICM and TE cells, compared with GDF9 or BMP15 treatment alone (P<0.05). In conclusion, the treatment of GDF9 or BMP15 (or both) enhanced the quality of blastocysts via the increased number of ICM and/or TE cells.

• Journal of Periodontal and Implant Science
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• 제49권2호
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• pp.90-104
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• 2019

Purpose: The aim of this study was to evaluate clinical and radiographic changes and the survival rate after periodontal surgery using deproteinized bovine bone mineral (DBBM) with 10% collagen or DBBM with a collagen membrane in endo-periodontal lesions. Methods: A total of 52 cases (41 patients) with at least 5 years of follow-up were included in this study. After scaling and root planing with or without endodontic treatment, periodontal regenerative procedures with DBBM with 10% collagen alone or DBBM with a collagen membrane were performed, yielding the DBBM + 10% collagen and DBBM + collagen membrane groups, respectively. Changes in clinical parameters including the plaque index, bleeding on probing, probing pocket depth, gingival recession, relative clinical attachment level, mobility, and radiographic bone gains were evaluated immediately before periodontal surgical procedures and at a 12-month follow-up. Results: At the 12-month follow-up after regenerative procedures, improvements in clinical parameters and radiographic bone gains were observed in both treatment groups. The DBBM + 10% collagen group showed greater probing pocket depth reduction ($4.52{\pm}1.06mm$) than the DBBM + collagen membrane group ($4.04{\pm}0.82mm$). However, there were no significant differences between the groups. Additionally, the radiographic bone gain in the DBBM + 10% collagen group ($5.15{\pm}1.54mm$) was comparable to that of the DBBM + collagen membrane group ($5.35{\pm}1.84mm$). The 5-year survival rate of the teeth with endo-periodontal lesions after periodontal regenerative procedures was 92.31%. Conclusions: This study showed that regenerative procedures using DBBM with 10% collagen alone improved the clinical attachment level and radiographic bone level in endo-periodontal lesions. Successful maintenance of the results after regenerative procedures in endo-periodontal lesions can be obtained by repeated oral hygiene education within strict supportive periodontal treatment.