• 제목/요약/키워드: APE

검색결과 66건 처리시간 0.019초

Ape1/Ref-1 Stimulates GDNF/GFR ${\alpha}$ 1-mediated Downstream Signaling and Neuroblastoma Proliferation

  • Kang, Mi-Young;Kim, Kweon-Young;Yoon, Young;Kang, Yoon-Sung;Kim, Hong-Beum;Youn, Cha-Kyung;Kim, Dong-Hui;Kim, Mi-Hwa
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제13권5호
    • /
    • pp.349-356
    • /
    • 2009
  • We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor ${\alpha}$ 1 (GFR ${\alpha}$ 1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFR ${\alpha}$ 1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFR ${\alpha}$ 1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFR ${\alpha}$ 1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFR ${\alpha}$ 1-specific RNA experiments demonstrated that the downregulation of GFR ${\alpha}$ 1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLC ${\gamma}$-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFR ${\alpha}$ signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.

전이학습 기반 기계번역 사후교정 모델 검증 (The Verification of the Transfer Learning-based Automatic Post Editing Model)

  • 문현석;박찬준;어수경;서재형;임희석
    • 한국융합학회논문지
    • /
    • 제12권10호
    • /
    • pp.27-35
    • /
    • 2021
  • 기계번역 사후교정 (Automatic Post Editing, APE)이란 번역 시스템을 통해 생성한 번역문을 교정하는 연구 분야로, 영어-독일어와 같이 학습데이터가 풍부한 언어쌍을 중심으로 연구가 진행되고 있다. 최근 APE 연구는 전이학습 기반 연구가 주로 이루어지는데, 일반적으로 self supervised learning을 통해 생성된 사전학습 언어모델 혹은 번역모델이 주로 활용된다. 기존 연구에서는 번역모델에 전이학습 시킨 APE모델이 뛰어난 성과를 보였으나, 대용량 언어쌍에 대해서만 이루어진 해당 연구를 저 자원 언어쌍에 곧바로 적용하기는 어렵다. 이에 본 연구에서는 언어 혹은 번역모델의 두 가지 전이학습 전략을 대표적인 저 자원 언어쌍인 한국어-영어 APE 연구에 적용하여 심층적인 모델 검증을 진행하였다. 실험결과 저 자원 언어쌍에서도 APE 학습 이전에 번역을 한차례 학습시키는 것이 유의미하게 APE 성능을 향상시킨다는 것을 확인할 수 있었다.

대기부유분진추출물로 야기된 DNA 손상에 대한 Quercetin, Vitamin C 및 Trolox 의 보호효과 (Chemopreventive Effect of Quercetin, Vitamin C and Trolox Against the Organic Extract of Airborne Particulate Matter Induced Genotoxicity in A549 Human Lung Carcinoma Cells)

  • 김남이;허문영
    • 약학회지
    • /
    • 제51권4호
    • /
    • pp.239-245
    • /
    • 2007
  • In order to evaluate the genotoxicity of airborne particulate matter extracted with dichloromethane (APE), the rat microsome mediated (S-9) or DNA repair enzyme treated Comet assays were performed using the single cell gel electrophoresis in A549 human lung carcinoma cells. It was found that the cells interacting with APE showed more DNA single-strand breaks relative to untreated cells. The genotoxicity of APE was increased with the treatment of S-9 mixture. Microsome mediated DNA damage was inhibited by CYP1Al inhibitor, quercetin. The APE also showed oxidative DNA damage evaluated by endonuclease III treatment. Oxidative DNA damage of APE was inhibited by antioxidants such as vita- min C and Trolox. We also found that the vegetables or fruits extract may reduce APE-induced genotoxicity by their anti- oxidant activity and CYP1A1 inhibition.

도토리박 추출물과 푸마르산 및 중온 열 병합처리에 의한 적근대의 미생물 제어 효과 (Combined Treatment of Acorn Pomace Extract, Fumaric Acid, and Mild Heat for Inactivation of Microorganisms on Red Chard)

  • 박신민;송경빈
    • 한국식품영양과학회지
    • /
    • 제45권11호
    • /
    • pp.1696-1700
    • /
    • 2016
  • 본 연구에서는 차아염소산 나트륨 같은 염소계 살균세척제를 대체하기 위한 천연 살균세척제로서 도토리박 추출물(APE)을 개발하기 위해 적근대에 Listeria monocytogenes를 접종한 후 APE의 항균 효과를 측정하였다. 그리고 최적 세척처리 조건을 수립하고자 APE, FA, $50^{\circ}C$에서의 mild heat를 병합처리하였다. 모든 처리구 중 0.5% APE/$50^{\circ}C$ mild heat/0.5% fumaric acid(FA) 병합 세척처리가 가장 효과적이었는데, L. monocytogenes 수를 대조구에 비해 3.36 log CFU/g 감소시켰다. 병합처리된 적근대 시료의 저장 8일 후 총 호기성균은 대조구와 비교하였을 때 2.89 log CFU/g 감소하였고, 색도 측정 결과 처리구 간 유의적인 차이가 나타나지 않았다. 따라서 본 연구 결과 APE/mild heat/FA 병합처리 방법은 수확 후 적근대의 품질에 영향을 미치지 않고 미생물학적 안전성을 높일 수 있는 효과적인 기술이라고 판단된다.

Evaluation of the antinociceptive activities of natural propolis extract derived from stingless bee Trigona thoracica in mice

  • Nurul Alina Muhamad Suhaini;Mohd Faeiz Pauzi;Siti Norazlina Juhari;Noor Azlina Abu Bakar;Jee Youn Moon
    • The Korean Journal of Pain
    • /
    • 제37권2호
    • /
    • pp.141-150
    • /
    • 2024
  • Background: Stingless bee propolis is a popular traditional folk medicine and has been employed since ancient times. This study aimed to evaluate the antinociceptive activities of the chemical constituents of aqueous propolis extract (APE) collected by Trigona thoracica in a nociceptive model in mice. Methods: The identification of chemical constituents of APE was performed using high-performance liquid chromatography (HPLC). Ninety-six male Swiss mice were administered APE (400 mg/kg, 1,000 mg/kg, and 2,000 mg/kg) before developing nociceptive pain models. Then, the antinociceptive properties of each APE dose were evaluated in acetic acid-induced abdominal constriction, hot plate test, and formalin-induced paw licking test. Administration of normal saline, acetylsalicylic acid (ASA, 100 mg/kg, orally), and morphine (5 mg/kg, intraperitoneally) were used for the experiments. Results: HPLC revealed that the APE from Trigona thoracica contained p-coumaric acid (R2 = 0.999) and caffeic acid (R2 = 0.998). Although all APE dosages showed inhibition of acetic acid-induced abdominal constriction, only 2,000 mg/kg was comparable to the result of ASA (68.7% vs. 73.3%, respectively). In the hot plate test, only 2,000 mg/kg of APE increased the latency time significantly compared to the control. In the formalin test, the durations of paw licking were significantly reduced at early and late phases in all APE groups with a decrease from 45.1% to 53.3%. Conclusions: APE from Trigona thoracica, containing p-coumaric acid and caffeic acid, exhibited antinociceptive effects, which supports its potential use in targeting the prevention or reversal of central and peripheral sensitization that may produce clinical pain conditions.

Clinical Characteristics, Risk Factors, and Outcomes of Acute Pulmonary Embolism in Thailand: 6-Year Retrospective Study

  • Pattarin Pirompanich;Ornnicha Sathitakorn;Teeraphan Suppakomonnun;Tunlanut Sapankaew
    • Tuberculosis and Respiratory Diseases
    • /
    • 제87권3호
    • /
    • pp.349-356
    • /
    • 2024
  • Background: Acute pulmonary embolism (APE) is a fatal disease with varying clinical characteristics and imaging. The aim of this study was to define the clinical characteristics, risk factors, and outcomes in patients with APE at a university hospital in Thailand. Methods: Patients diagnosed with APE and admitted to our institute between January 1, 2017 and December 31, 2022 were retrospectively enrolled. The clinical characteristics, investigations, and outcomes were recorded. Results: Over the 6-year study period, 369 patients were diagnosed with APE. The mean age was 65 years; 64.2% were female. The most common risk factor for APE was malignancy (46.1%). In-hospital mortality rate was 23.6%. The computed tomography pulmonary artery revealed the most proximal clots largely in segmental pulmonary artery (39.0%), followed by main pulmonary artery (36.3%). This distribution was consistent between survivors and non-survivors. Multivariate logistic regression analysis revealed that APE mortality was associated with active malignancy, higher serum creatinine, lower body mass index (BMI), and tachycardia with adjusted odds ratio (95% confidence interval [CI]) of 3.70 (1.59 to 8.58), 3.54 (1.35 to 9.25), 2.91 (1.26 to 6.75), and 2.54 (1.14 to 5.64), respectively. The prediction model was constructed with area under the curve of 0.77 (95% CI, 0.70 to 0.84). Conclusion: The overall mortality rate among APE patients was 23.6%, with APE-related death accounting for 5.1%. APE mortality was associated with active malignancy, higher serum creatinine, lower BMI, and tachycardia.

Identification of New Potential APE1 Inhibitors by Pharmacophore Modeling and Molecular Docking

  • Lee, In Won;Yoon, Jonghwan;Lee, Gunhee;Lee, Minho
    • Genomics & Informatics
    • /
    • 제15권4호
    • /
    • pp.147-155
    • /
    • 2017
  • Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.

기계번역 사후교정(Automatic Post Editing) 연구 (Automatic Post Editing Research)

  • 박찬준;임희석
    • 한국융합학회논문지
    • /
    • 제11권5호
    • /
    • pp.1-8
    • /
    • 2020
  • 기계번역이란 소스문장(Source Sentence)을 타겟문장(Target Sentence)으로 컴퓨터가 번역하는 시스템을 의미한다. 기계번역에는 다양한 하위분야가 존재하며 APE(Automatic Post Editing)이란 기계번역 시스템의 결과물을 교정하여 더 나은 번역문을 만들어내는 기계번역의 하위분야이다. 즉 기계번역 시스템이 생성한 번역문에 포함되어 있는 오류를 수정하여 교정문을 만드는 과정을 의미한다. 기계번역 모델을 변경하는 것이 아닌 기계번역 시스템의 결과 문장을 교정하여 번역품질을 높이는 연구분야이다. 2015년부터 WMT 공동 캠페인 과제로 선정되었으며 성능 평가는 TER(Translation Error Rate)을 이용한다. 이로 인해 최근 APE에 모델에 대한 다양한 연구들이 발표되고 있으며 이에 본 논문은 APE 분야의 최신 동향에 대해서 다루게 된다.

비소세포 폐암조직에시 Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-1의 발현변화 (Alteration of Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-1 in Human Mon-small Cell Lung Cancer)

  • 유대군;송윤정;조은정;강민웅;한종희;나명훈;임승평;유재현;전병화;이영
    • Journal of Chest Surgery
    • /
    • 제40권8호
    • /
    • pp.529-535
    • /
    • 2007
  • 배경: 산화제와 항산화제 사이의 불균형은 폐암의 발생에 중요한 역할을 하는 것으로 생각되는 산화 스트레스를 유발한다. APE/ref-1은 DNA의 복구와 많은 전사인자들의 산화환원 조절에 연관된 다 기능성 단백질이다. 그러나 폐암에서 APE/ref-1 발현수준의 변화는 알려져 있지 않다. 대상 및 방법: 49명의 수술적으로 제거한 비소세포성 폐암 환자를 대상으로 하였다. APE/ref-1 항체에 대한 면역조직화학적 염색을 하였고, 특이 항체에 대한 Western blot을 시행해 발현 정도를 분석하였다. 결과: APE/ref-1은 주로 폐암 조직의 비 암세포 부분은 핵에 국한되어 존재하였고, 암세포는 핵과 세포질 모두에 존재하였다. 비소세포성 폐암의 핵과 세포질의 APE/ref-1의 발현은 증가되어 있었고 이는 임상적인 병기와도 상관관계를 보였다. 대표적인 항산화 물질인 catalase는 비소세포성 폐암에서 현격하게 감소되어 있었다. 결론: APE/ref-1, 특히 세포질 내의 APE/ref-1의 증가는 산화스트레스에 보상적으로 일어나는 것으로 생각하며 catalase의 감소는 폐암의 특성을 나타내는 세포 외부의 산화환원과정에 근본적인 역할을 하는 것으로 생각한다.

Association of DNA Base-excision Repair XRCC1, OGG1 and APE1 Gene Polymorphisms with Nasopharyngeal Carcinoma Susceptibility in a Chinese Population

  • Li, Qing;Wang, Jian-Min;Peng, Yu;Zhang, Shi-Heng;Ren, Tao;Luo, Hao;Cheng, Yi;Wang, Dong
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제14권9호
    • /
    • pp.5145-5151
    • /
    • 2013
  • Background: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles. Aims: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. Materials and Methods: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models. Results: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02-3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1-141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants, was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004). Conclusion: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1-141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.