• Title/Summary/Keyword: APE

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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
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    • v.13 no.5
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    • pp.349-356
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    • 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.

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

  • Moon, Hyeonseok;Park, Chanjun;Eo, Sugyeong;Seo, Jaehyung;Lim, Heuiseok
    • Journal of the Korea Convergence Society
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    • v.12 no.10
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    • pp.27-35
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    • 2021
  • Automatic post editing is a research field that aims to automatically correct errors in machine translation results. This research is mainly being focus on high resource language pairs, such as English-German. Recent APE studies are mainly adopting transfer learning based research, where pre-training language models, or translation models generated through self-supervised learning methodologies are utilized. While translation based APE model shows superior performance in recent researches, as such researches are conducted on the high resource languages, the same perspective cannot be directly applied to the low resource languages. In this work, we apply two transfer learning strategies to Korean-English APE studies and show that transfer learning with translation model can significantly improves APE performance.

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

  • Kim, Nam-Yee;Heo, Moon-Young
    • YAKHAK HOEJI
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    • v.51 no.4
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    • pp.239-245
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    • 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.

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

  • Park, Shin-Min;Son, Kyung Bin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.11
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    • pp.1696-1700
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    • 2016
  • In this study, acorn pomace extract (APE) was developed as a natural chemical sanitizer and substitute for chlorine-based sanitizers such as sodium hypochlorite containing harmful substances. Antimicrobial activities of APE and its combined treatments with fumaric acid (FA) and mild heat against Listeria monocytogenes inoculated on red chard were examined. Among the treatments, combined treatment of 0.5% APE at $50^{\circ}C$ and 0.5% FA was the most effective, causing reduction of L. monocytogenes populations by 3.36 log CFU/g compared to the control. After combined treatment, populations of aerobic mesophilic bacteria in the red chard decreased by 2.89 log CFU/g during storage at $4^{\circ}C$ for 8 days compared to the control. Regarding color changes in red chard upon combined treatment, there was no significant change among the red chard samples. These results indicate that combined treatment of APE, FA, and mild heat can improve microbial safety of red chard without affecting quality such as color during storage.

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
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    • v.37 no.2
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    • pp.141-150
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    • 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
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    • v.87 no.3
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    • pp.349-356
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    • 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
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    • v.15 no.4
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    • pp.147-155
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    • 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.

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

  • Park, Chan-Jun;Lim, Heui-Seok
    • Journal of the Korea Convergence Society
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    • v.11 no.5
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    • pp.1-8
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    • 2020
  • Machine translation refers to a system where a computer translates a source sentence into a target sentence. There are various subfields of machine translation. APE (Automatic Post Editing) is a subfield of machine translation that produces better translations by editing the output of machine translation systems. In other words, it means the process of correcting errors included in the translations generated by the machine translation system to make proofreading. Rather than changing the machine translation model, this is a research field to improve the translation quality by correcting the result sentence of the machine translation system. Since 2015, APE has been selected for the WMT Shaed Task. and the performance evaluation uses TER (Translation Error Rate). Due to this, various studies on the APE model have been published recently, and this paper deals with the latest research trends in the field of APE.

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

  • Yoo, Dae-Goon;Song, Yun-Jeong;Cho, Eun-Jung;Kang, Min-Woong;Han, Jong-Hee;Na, Myung-Hoon;Lim, Seung-Pyung;Yu, Jae-Hyeon;Jeon, Byeong-Hwa;Lee, Young
    • Journal of Chest Surgery
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    • v.40 no.8
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    • pp.529-535
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    • 2007
  • Background: An imbalance between oxidants and antioxidants leads to oxidative stress, and this has been proposed to play an important role in the pathogenesis of lung neoplasm. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) is a multifunctional protein involved in DNA base excision repair and the redox regulation of many transcription factors. However, the alteration of the expressed levels of APE/ref-1 in non-small cell lung cancer is unknown. Material and Method: Forty-nine patients with surgically resected non-small cell lung cancer (NSCLC) were included in this study. Immunohistochemical staining with APE/ref-1 antibodies was performed, and their expressions were analyzed via Western blotting for specific antibodies. Result: APE/ref-1 was localized at the nucleus and mainly in the non-tumor region of the NSCLC tissue specimens; it was expressed in the cytoplasm and nucleus of the NSCLC. The nuclear and cytoplasmic expressions of APE/ref-1 in lung cancers were markedly up-regulated in the NSCLC, and this was correlated with the clinical stage. Catalase, as first-line antioxidant defense, was dramatically decreased in the NSCLC. Conclusion: Taken together, our results suggest that APE/ref-1, and especially cytoplasmic APE/ref-1, was upregulated in the lung cancer regions, and this may contribute to the compensatory defense system against oxidative stress. A low expression of catalase might have fundamental effects on the extracellular redox state of lung tumors, along with the potential consequences for the tumors.

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
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    • v.14 no.9
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    • pp.5145-5151
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    • 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.