• 생명과학회지
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• 제32권1호
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• pp.63-69
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• 2022

Thioredoxin reductase (TrxR) 시스템은 세포 내 산화 환원 반응의 항상성 유지와 신호 전달 경로를 조절하는데 중추적인 역할을 함으로써 세포의 생존과 기능 유지에 필수적이다. TrxR 시스템은 thioredoxin (Trx), TrxR 및 nicotinamide adenine dinucleotide phosphate의 구성요소를 포함하며, TrxR 효소의 촉매 반응에 의해 환원된 Trx는 하위 표적 단백질을 환원시켜 결과적으로 산화적 스트레스에 대한 방어와 세포 분화, 성장 및 사멸을 조절한다. 암세포는 무한한 세포 증식과 높은 대사율로 인해 과도하게 생성된 활성산소종을 소거하기 위해 세포 내 항산화능을 향상시켜 세포의 생존을 유지하는 반면, 항산화 시스템에 대한 의존도 및 민감도가 높아 이를 표적으로 한 항암 활성 연구에서 잠재적인 가능성이 있음을 제시한다. 여러 연구 결과에서 TrxR이 다양한 유형의 암에서 높은 수준으로 발현되고 있음이 밝혀졌고, 또한 TrxR 시스템을 표적으로 한 항암 활성에 대한 연구가 증가하고 있다. 따라서 본 총설에서는 세포 내 TrxR 시스템의 기능과 암의 발달 및 진행에서의 역할을 다루고, TrxR 억제제의 항암 활성 및 기전을 검토함으로써 항암 활성 연구에 대한 전략으로 TrxR 시스템의 타당성과 가치를 논하였다.

• Journal of Photoscience
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• 제9권2호
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• pp.518-520
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• 2002

Photodynamic therapy (PDT) is a treatment modality based on photochemical reaction and the resultant cytotoxic reactive oxygen species. The platelet thrombus formation leading to stasis observed in vivo during PDT is called vascular shut down (VSD) effect. To investigate the mechanism of the VSD effect, we observed Human Umblical Vein Endothelial Cell (HUVEC) injury induced by photochemical reaction. We observed cell retraction and blebbing after PDT. It seems that the injury was not fetal and only morphological change. Then, the cytoplasm was stained by Calcein-AM and subendothelial area was evaluated from fluorescence microscopy. The rate of subendothelial area after PDT increased significantly. Second, we investigated interaction between neutrophils and HUVEC. Human promyelocytic leukemia cells (HL-60) were differentiated into neutrophil by incubation with all-trans retinoic acid. Calcein-AM labeled neutrophil adhesion to HUVEC was evaluated from fluorescence microscopy. PDT-induced neutrophil adhesion to HUVEC depended more on the exposure of subendothlial area than on neutrophil activation. This result suggests that there is a certain interaction between neutrophil and HUVEC during PDT.

• 대한한방소아과학회지
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• 제29권4호
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• pp.77-89
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• 2015

Objectives The purpose of this study is to analyze Korean clinical studies in Korean medicine and complementary and alternative medicine for allergic rhinitis and to propose for better methods of clinical studies and effective treatments on allergic rhinitis. Methods Electronic researches were performed with NDSL, RISS, KISTI, KISS, OASIS by keyword 'Allergic rhinitis'. Results The treatments used in 36 studies were herbal medicines, acupuncture, pharmacopuncture, moxibustion, cupping, inject medicine to nasal cavity, aroma therapy, ointment, nasal cleansing solution, laser treatment, infra-red therapy, oxygen nebulizer, diet treatment, moxa-pellet treatment, mindfulness meditation and space-spine manipulation techniques. The most common acupoints were LI4 and LI20 (Large Intestine Meridian). The most common methods of assessment is subjective nasal symptoms. All studies using subjective nasal symptoms and quality of life as assessment methods to show valid results on the improvement of allergic rhinitis. Conclusions This study shows that Korean medicine and complementary and alternative medicine on allergic rhinitis are effective. It will be expected to use that various methods for allergic rhinitis and more clinical studies for allergic rhinitis and pediatric patients needed in the future.

• Biomolecules & Therapeutics
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• 제26권1호
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• pp.29-38
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• 2018

During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation. Thus, metabolic reprogramming of NADPH homeostasis is an important step in cancer progression as well as in combinational therapeutic approaches. In mammalian, the pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of NADPH production. In this review, we focus on the importance of glucose flux control towards PPP regulated by oncogenic pathways and the potential therein for metabolic targeting as a cancer therapy. We also summarize the role of Snail (Snai1), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress.

• 대한수의학회지
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• 제44권1호
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• pp.125-129
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• 2004

A 2-year-old, female, American cocker spaniel dog presented for a 1-year history of severe ascites, exercise intolerance, tachypnea. At that time, she was in an emergency state. First, the dog was stabilized with oxygen therapy. A diagnosis of cardiac problem was made from history, auscultation, radiograph, ECG, and echocardiography. Jugular pulsation was palpated and a harsh, systolic murmur of tricuspid regurgitation was prominent at the right cardiac apex. Tricuspid valve dysplasia (TVD) was confirmed with echocardiography, accompanying enormous myocardial hypertrophy. The clinical signs had been improved for 8 months with careful therapy and periodic abdominocentesis, and ascites was well controlled. The situation, however, became worse quickly in a week because the client did not follow our management schedule. Finally, she died due to dyspnea and shock. After the spontaneous death, necropsy and histopathological examination were performed and when we opened the thorax, a significantly large heart was observed. On histopathological findings, grossly myocardium appeared pale initially, then progressed to yellow and white. Microscopically, there was an extensive hemorrhage along with loss of myocardial striations. Interstitial fibrosis and various degenerative alterations in myocytes were also present.

• International Journal of Oral Biology
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• 제41권2호
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• pp.69-74
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• 2016

Skin-derived precursors (SKPs) have potential to differentiate to various cell types including osteoblasts, adipocytes and neurons. SKPs are a candidate for cell-based therapy since they are easily accessible and have multipotency. Most mammalian cells are exposed to a low oxygen environment with 1 to 5% $O_2$ concentration in vivo, while 21% $O_2$ concentration is common in in vitro culture. The difference between in vitro and in vivo $O_2$ concentration may affect to the behavior of cultured cells. In this report, we investigated the effect of hypoxic condition on stemness and proliferation of SKPs. The results indicated that SKPs exposed to hypoxic condition for 5 days showed no change in proliferation. In terms of mRNA expression, hypoxia maintained expression of stemness markers; whereas, oncogenes, such as Klf4 and c-Myc, were downregulated, and the expression of Nestin, related to cancer migration, was also downregulated. Thus, SKPs cultured in hypoxia may reduce the risk of cancer in SKP cell-based therapy.

• Molecules and Cells
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• 제46권3호
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• pp.153-164
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• 2023

Cancer stem cells (CSCs) are a small population of tumor cells characterized by self-renewal and differentiation capacity. CSCs are currently postulated as the driving force that induces intra-tumor heterogeneity leading to tumor initiation, metastasis, and eventually tumor relapse. Notably, CSCs are inherently resistant to environmental stress, chemotherapy, and radiotherapy due to high levels of antioxidant systems and drug efflux transporters. In this context, a therapeutic strategy targeting the CSC-specific pathway holds a promising cure for cancer. NRF2 (nuclear factor erythroid 2-like 2; NFE2L2) is a master transcription factor that regulates an array of genes involved in the detoxification of reactive oxygen species/electrophiles. Accumulating evidence suggests that persistent NRF2 activation, observed in multiple types of cancer, supports tumor growth, aggressive malignancy, and therapy resistance. Herein, we describe the core properties of CSCs, focusing on treatment resistance, and review the evidence that demonstrates the roles of NRF2 signaling in conferring unique properties of CSCs and the associated signaling pathways.

• 대한의생명과학회지
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• 제30권1호
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• pp.10-16
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• 2024

Oxidative stress caused by elevated reactive oxygen species (ROS) in the heart causes various heart diseases. Oxidative stress is known as a factor that causes diseases in various organs as well as the heart. Diseases such as heart failure, myocardial infarction, and cardiomyopathy caused by oxidative stress in the heart can be treated with medication or surgery. Recently, blood cells concentrate (BCC) is used in various treatment areas such as orthopedics, gynecology, and urology. BCC therapy is applied to treatment by concentrating platelets and white blood cells necessary for regeneration through simple centrifugation using autologous blood. As the platelets are activated, many growth factors are released from alpha granules of the platelets. Growth factors such as TGF-β1, PDGF, VEGF, and EGF derived from platelets are involved in various cell signaling pathway. Due to these growth factors, BCC can contribute to tissue regeneration and can treat various diseases. CD34+ cells contained in BCC may also play an important role in tissue regeneration. In this study, we investigated whether BCC has a regenerative effect on heart disease, and if so, what mechanism causes the effect. To observe this, cardiomyocyte cells were treated with H₂O₂ to induce oxidative stress. And the effect was confirmed in the presence or absence of BCC. As a result, in the presence of BCC, the oxidative stress of cardiomyocyte cells was reduced and cell damage was also reduced. These results suggest that BCC therapy can be a new treatment alternative for heart disease.

• Tuberculosis and Respiratory Diseases
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• 제45권6호
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• pp.1223-1235
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• 1998

연구배경 : 급성호흡곤란증후군(ARDS) 환자의 폐 산소화를 개선시키기 위한 보조적 치료법인 복와위 자세에서의 인공환기는 대상 환자의 약 61%에서, 흡입 산화질소 투여는 60-80%에서 효과가 있는 것으로 보고되어 있다. 산소화 호전의 주된 기전은 복와위시는 이환이 심한 등쪽 폐의 환기 호전에 의한 단락 감소이며, 산화질소 투여 시는 이환부위로부터 정상 폐포로의 폐 혈류의 재분포에 의한 단락 감소안 것으로 알려져 있다. 그러므로 복와위와 산화질소의 병용 치료 시 산소화 개선에 상승 효과를 기대할 수 있으나 이에 관한 임상 연구는 없었다. 이에 저자들은 ARDS환자에서 두 치료의 병합이 가스 교환 및 혈류 역학에 미치는 영향을 관찰하였다. 방 법 : ARDS 환자 12명(연령 $56{\pm}12$ 세, 남 : 여=9 : 3)을 대상으로 앙와위에서 호흡 및 혈류역학적 지표를 측정한 후 복와위로 전환하였다. 복와위 30분과 2시간에 동일 지표들을 측정한 뒤 산화질소를 투여하고 (5-10 ppm), 이후 30분, 2 시간 및 산화질소 투여 중단 후 10분에 각각 동일 지표들을 재 측정하였다. 결 과 : 가스 교환 지표 : 복와위에서 산화질소 병용 치료시, 앙와위 및 복와위에서보다 $PaO_2/FiO_2$가 증가되었고(각각 p< 0.01) 폐동맥혈 산소분압차($AaDO_2$)는 감소하였다(각각 p<0.005). 호흡 역학적 지표 : 폐 탄성, 호흡기계 탄성, 기도 저항 및 흡기말 기도압은 치료 방법에 따른 차이가 없었다. 혈류 역학적 지표 : 복와위에서 산화질소 병용 치료시, 앙와위 및 복와위에서보다 심 박출량 및 조직산소전달량($DO_2$)이 증가되었으며(각 P< 0.05), 폐혈관 저항, 평균 폐동맥압 및 폐동맥쐐기압은 감소되었다(각 P< 0.05). 결 론 : 급성호흡곤란증후군 환자에서 복와위 및 산화질소 홉업의 병용 치료는 복와위 단독 치료에 비해 폐산소화 호전에 상승 작용이 있으며, 조직으로의 산소 전달량도 증가시키므로 급성호흡곤란증후군 환자의 보조적인 치료법으로써 유용할 것으로 사료되었다.

• Journal of Microbiology and Biotechnology
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• 제27권10호
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• pp.1877-1884
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• 2017

Mesenchymal stem cells (MSCs) have been suggested as a primary candidate for cell therapy applications because they have self-renewal and differentiation capabilities. Although they can be expanded in ex vivo system, clinical application of these cells is still limited because they survive poorly and undergo senescence or apoptosis when transplanted and exposed to environmental factors such as oxidative stress. Thus, reducing oxidative stress is expected to improve the efficacy of MSC therapy. The milk protein lactoferrin is a multifunctional iron-binding glycoprotein that plays various roles, including reduction of oxidative stress. Thus, we explored the effect of lactoferrin on oxidative stress-induced senescence and apoptosis of human MSCs (hMSCs). Measurement of reactive oxygen species (ROS) revealed that lactoferrin inhibited the production of hydrogen peroxide-induced intracellular ROS, suggesting lactoferrin as a good candidate as an antioxidant in hMSCs. Pretreatment of lactoferrin suppressed hydrogen peroxide-induced senescence of hMSCs. In addition, lactoferrin reduced hydrogen peroxide-induced apoptosis via inhibition of caspase-3 and Akt activation. These results demonstrate that lactoferrin can be a promising factor to protect hMSCs from oxidative stress-induced senescence and apoptosis, thus increasing the efficacy of MSC therapy.