• BMB Reports
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• 제53권5호
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• pp.284-289
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• 2020

Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine against tamoxifen-induced RPE cell death. Tamoxifen induced reactive oxygen species (ROS)-mediated autophagic cell death and caspase-1-mediated pyroptosis in RPE cells. However, sulfasalazine reduced tamoxifen-induced total ROS and ROS-mediated autophagic RPE cell death. Also, mRNA levels of tamoxifen-induced pyroptosis-related genes, IL-1β, NLRP3, and procaspase-1, also decreased in the presence of sulfasalazine in RPE cells. Additionally, the mRNA levels of tamoxifen-induced AMD-related genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), apolipoprotein J (APOJ), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), were downregulated in RPE cells. Together, these data provide novel insight into the therapeutic effects of sulfasalazine against tamoxifen-induced RPE cell death.

• 생명과학회지
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• 제21권1호
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• pp.9-14
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• 2011

심박수(heart rate) 및 산소 소비량(oxygen consumption) 등의 생리학적 변수는 운동자각도(RPE)와 밀접한 관련이 있으며, RPE의 남녀차이에 의한 예측 운동강도의 정확성은 아직 밝혀지지 않고 있고, 본 연구는 남녀 대학생의 심장 혈관 및 신진대사의 반응을 평가하고 남녀의 차이를 밝히는 데 있다. 남자대학생($25.1{\pm}1.56$ yr)과 여자대학생($25.0{\pm}4.12$ yr) 각각 10명이 본 연구에 자발적으로 참여를 하였고, 본 연구를 위하여 설정된RPE는 Borg의 15 범주에서 결정을 하였으며, 점증적 운동부하(graded exercise testing)는 Bruce Treadmill Protocol을 이용하였다. 남녀의 평균 slope (p=0.501)와 RPE의 plotting rates와 최대산소섭취율(% $VO_2$max)은 유의한 차이가 나타나지 않았다. 각자의 상대적 최대산소섭취량은 남학생의 경우52.36${\pm}$7.35 ml/kg/min, 여학생은 41.44${\pm}$6.71 ml/kg/min로 나타나 두 그룹간에 유의하게 큰 차이가 있었으며, 절대적 최대산소섭취량은 남학생은 4.05${\pm}$0.36 l/min, 여학생은 2.53${\pm}$0.39 l/min로 나타나 두 그룹간에 큰 차이가 나타냈다. 남학생과 여학생간의 slope, y-intercept, SEE는 통계적으로 유의한 차이는 없었다. 본 연구에서 운동강도에 따른 남학생과 여학생의 RPE 의 차이는 유의하게 나타나지 않았다. 이상의 결과로 보아 RPE는 운동중 산소섭취량에 대한 운동강도의 예측에 남녀별 차이가 없어 유효한 예측인자라고 사료된다.

• Molecules and Cells
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• 제46권7호
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• pp.441-450
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• 2023

β-Catenin (Ctnnb1) has been shown to play critical roles in the development and maintenance of epithelial cells, including the retinal pigment epithelium (RPE). Ctnnb1 is not only a component of intercellular junctions in the epithelium, it also functions as a transcriptional regulator in the Wnt signaling pathway. To identify which of its functional modalities is critically involved in mouse RPE development and maintenance, we varied Ctnnb1 gene content and activity in mouse RPE lineage cells and tested their impacts on mouse eye development. We found that a Ctnnb1 double mutant (Ctnnb1^dm), which exhibits impaired transcriptional activity, could not replace Ctnnb1 in the RPE, whereas Ctnnb1^Y654E, which has reduced affinity for the junctions, could do so. Expression of the constitutively active Ctnnb1^∆ex3 mutant also suppressed the development of RPE, instead facilitating a ciliary cell fate. However, the post-mitotic or mature RPE was insensitive to the loss, inactivation, or constitutive activation of Ctnnb1. Collectively, our results suggest that Ctnnb1 should be maintained within an optimal range to specify RPE through transcriptional regulation of Wnt target genes in the optic neuroepithelium.

• Clinical and Experimental Reproductive Medicine
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• 제38권4호
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• pp.216-221
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• 2011

Objective: To differentiate the human embryonic stem cells (hESCs) into the retinal pigment epithelium (RPE) in the defined culture condition and determine its therapeutic potential for the treatment of retinal degenerative diseases. Methods: The embryoid bodies were formed from hESCs and attached on the matrigel coated culture dishes. The neural structures consisting neural precursors were selected and expanded to form rosette structures. The mechanically isolated neural rosettes were differentiated into pigmented cells in the media comprised of N2 and B27. Expression profiles of markers related to RPE development were analyzed by reverse transcription-polymerase chain reaction and immunostaining. Dissociated putative RPE cells ($10^5$ cells/5 ${\mu}L$) were transplanted into the subretinal space of rat retinal degeneration model induced by intravenous sodium iodate injection. Animals were sacrificed at 1, 2, and 4 weeks after transplantation, and immnohistochemistry study was performed to verify the survival of the transplanted cells. Results: The putative RPE cells derived from hESC showed characteristics of the human RPE cells morphologically and expressed molecular markers and associated with RPE fate. Grafted RPE cells were found to survive in the subretinal space up to 4 weeks after transplantation, and the expression of RPE markers was confirmed with immunohistochemistry. Conclusion: Transplanted RPE cells derived from hESC in the defined culture condition successfully survived and migrated within subretinal space of rat retinal degeneration model. These results support the feasibility of the hESC derived RPE cells for cell-based therapies for retinal degenerative disease.

• 한국음향학회:학술대회논문집
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• 한국음향학회 1995년도 제12회 음성통신 및 신호처리 워크샵 논문집 (SCAS 12권 1호)
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• pp.164-167
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• 1995

RPE 음성부호화기에서 합성 필터로 인한 구동벡터 양자화잡음의 증폭효과를 분석하고 regular pulse 시퀀스의 양자화로 인한 성능감쇄를 줄이기 위해 pyramid vector 양자화방식을 도입하였다. 제안된 방식의 성능평가는 구동시퀀스 양자화를 위해 adaptive PCM을 이용하는 GSM 표준 RPE 방식과의 객관적 및 주관적 성능비교를 통해 수행하였다.T JDSMDQLRY 결과 제안된 방식은 대략 1dB의 SNR 및 segmental SNR 값 증가를 가져왔고, 또한 비공식 청취시험결과 명료도의 증가를 느낄 수 있었다.

• BMB Reports
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• 제56권2호
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• pp.84-89
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• 2023

The implications of nutrient starvation due to aging on the degeneration of the retinal pigment epithelium (RPE) is yet to be fully explored. We examined the involvement of AMPK activation in mitochondrial homeostasis and its relationship with the maintenance of a healthy mitochondrial population and epithelial characteristics of RPE cells under nutrient starvation. Nutrient starvation induced mitochondrial senescence, which led to the accumulation of reactive oxygen species (ROS) in RPE cells. As nutrient starvation persisted, RPE cells underwent pathological epithelial-mesenchymal transition (EMT) via the upregulation of TWIST1, a transcription regulator which is activated by ROS-induced NF-κB signaling. Enhanced activation of AMPK with metformin decelerated mitochondrial senescence and EMT progression through mitochondrial biogenesis, primed by activation of PGC1-α. Thus, by facilitating mitochondrial biogenesis, AMPK protects RPE cells from the loss of epithelial integrity due to the accumulation of ROS in senescent mitochondria under nutrient starvation.

• 폴리머
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• 제38권1호
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• pp.24-30
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• 2014

망막색소상피(retinal pigment epithelium, RPE)는 시기능을 유지하는데 중요한 역할을 하여 RPE의 퇴화는 여러 망막변성질병을 유발한다. 현재 이에 대한 효과적인 치료법이 부족하여 세포 이식에 적합한 지지체를 제작하기 위해, 생분해성 고분자인 PLGA와 항염증, 항산화 작용 등의 기능이 있는 헤스페리딘을 이용하여 하이브리드 필름을 제조하였다. ARPE-19를 파종한 후, MTT 분석법을 이용하여 세포 증식률을 확인하고, 세포의 부착 및 세포 형태를 SEM을 통하여 확인하였다. 또한 RPE 세포의 특이적 유전자 발현정도를 확인하기 위하여 RT-PCR을 수행하였고, RPE65의 발현을 확인하기 위해 AEC 면역화학적 염색을 실시하였다. 그 결과, 헤스페리딘/PLGA 필름은 PLGA보다 RPE 세포의 부착, 증식 및 표현형 유지가 우수함을 확인하였고, 이를 통해 헤스페리딘/PLGA 필름의 망막재생을 위한 조직공학적 담체로써 응용 가능성을 확인할 수 있었다.

• 폴리머
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• 제26권1호
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• pp.37-44
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• 2002

폐폴리염화비닐수지(waste Polyvinyl chloride, RPVC)와 폐폴리에틸렌수지(waste polyethylene, RPE)의 블렌드를 용융 혼합으로 제조하였으며 상용화제로서 주쇄는 에틸렌 구조를, 측쇄는 에스터 그룹으로 이루어진 공중합체들을 첨가하여 모폴로지 및 인장특성에 미치는 영향을 조사하였다. RPVC가 연속상인 조성비 85/15 wt%, 중간조성 50/50 wt%, RPE가 연속상인 조성비 15/85 wt%로 RPVC/RPE의 조성비를 변화시켜 이들 조성비에서의 상용화제의 영향을 조사하였다. 모폴로지 관찰로 볼 때 RPVC/RPE 블렌드는 $10\mu\textrm{m}$ 이상의 도메인 크기를 보여 상용성이 나쁘며 특히 중간조성에서 가장 나쁜 상용성을 나타내었다. 에틸렌비닐아세테이트 공중합체(EVA)와 에틸렌에틸아크릴레이트 메틸메타크릴레이트 그라프트 공중합체 (ethylene ethylacrylate-graft-methyl methacrylate copolymer, EEA-MMA)가 상용화제로서 우수한 결과를 나타내었다.

• Journal of Medicine and Life Science
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• 제18권3호
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• pp.61-65
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• 2021

Although re-expansion pulmonary edema (RPE) is rare (incidence rate <1%), it is associated with a mortality rate of >20%; therefore, early diagnosis and treatment are important. We report a case of RPE following chest tube insertion in a patient with spontaneous pneumothorax. We have specifically focused on the mechanism underlying RPE and the possible etiology. An 82-year-old man with a history of chronic anemia, chronic obstructive pulmonary disease, diabetes mellitus, and hypertension was referred to the emergency department for management of recurrent right-sided pneumothorax. We performed emergency closed thoracostomy for suspected tension pneumothorax, which led to stabilization of the patient's vital signs; however, he coughed up frothy pink sputum accompanied by severe right-sided chest pain 30 min postoperatively. The patient showed new-onset right pulmonary consolidation on chest radiography, as well as desaturation, tachycardia, and tachypnea and was diagnosed with RPE. He was transferred to the intensive care unit for mechanical ventilation and supportive treatment using diuretics, ionotropic agents, and prophylactic antibiotics. RPE gradually resolved, and the patient was extubated 3 days after admission. He has not experienced recurrent pneumothorax or pulmonary disease for 4 months. We emphasize the importance of RPE prevention and that aggressive ventilator care and supportive treatment can effectively treat RPE following an accurate understanding of the underlying pathogenetic mechanisms and risk factors.

• Molecules and Cells
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• 제44권8호
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• pp.591-601
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• 2021

Cilia are highly specialized organelles that extend from the cell membrane and function as cellular signaling hubs. Thus, cilia formation and the trafficking of signaling molecules into cilia are essential cellular processes. TULP3 and Tubby (TUB) are members of the tubby-like protein (TULP) family that regulate the ciliary trafficking of G-protein coupled receptors, but the functions of the remaining TULPs (i.e., TULP1 and TULP2) remain unclear. Herein, we explore whether these four structurally similar TULPs share a molecular function in ciliary protein trafficking. We found that TULP3 and TUB, but not TULP1 or TULP2, can rescue the defective cilia formation observed in TULP3-knockout (KO) hTERT RPE-1 cells. TULP3 and TUB also fully rescue the defective ciliary localization of ARL13B, INPP5E, and GPR161 in TULP3 KO RPE-1 cells, while TULP1 and TULP2 only mediate partial rescues. Furthermore, loss of TULP3 results in abnormal IFT140 localization, which can be fully rescued by TUB and partially rescued by TULP1 and TULP2. TUB's capacity for binding IFT-A is essential for its role in cilia formation and ciliary protein trafficking in RPE-1 cells, whereas its capacity for PIP₂ binding is required for proper cilia length and IFT140 localization. Finally, chimeric TULP1 containing the IFT-A binding domain of TULP3 fully rescues ciliary protein trafficking, but not cilia formation. Together, these two TULP domains play distinct roles in ciliary protein trafficking but are insufficient for cilia formation in RPE-1 cells. In addition, TULP1 and TULP2 play other unknown molecular roles that should be addressed in the future.