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      • KCI등재

        A Novel EYA1 Mutation Causing Alternative RNA Splicing in a Chinese Family With Branchio-Oto Syndrome: Implications for Molecular Diagnosis and Clinical Application

        Anhai Chen,Chufeng He,Yong Feng,Jie Ling,Xin Peng,Xianlin Liu,Shuang Mao,Yongjia Chen,Mengyao Qin,Shuai Zhang,Yijiang Bai,Jian Song,Zhili Feng,Lu Ma,Dinghua He,Lingyun Mei1 대한이비인후과학회 2023 Clinical and Experimental Otorhinolaryngology Vol.16 No.4

        Objectives. Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However,few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenicfactors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in thesepatients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the ge-netic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods. We collected detailed clinical features and peripheral blood samples from the patients and unaffected individualswithin the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis andclassified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing wasverified through a minigene assay. The predicted three-dimensional protein structure and biochemical experimentswere used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was fol-lowed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results. A novel heterozygous EYA1 splicing variant (c.1050+4 A >C) was identified and classified as pathogenic (PVS1(RNA),PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation mayimpair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellularmislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improvedhearing loss caused by bone-conduction abnormalities in the proband. Conclusion. We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molec-ular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgeryprovides a reference for auditory rehabilitation in similar patients.

      • KCI등재

        Camptothecin activates SIRT1 to promote lipid catabolism through AMPK/FoxO1/ATGL pathway in C2C12 myogenic cells

        Mei-Chen Lo,Jia-Yin Chen,Yung-Ting Kuo,Wei-Lu Chen,Horng-Mo Lee,Shyang-Guang Wang 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.8

        Caloric restriction activates sirtuin 1 (SIRT1)and induces a variety of metabolic effects that are beneficialfor preventing age-related disease. The present studyscreened a commercially available used drug library todevelop small molecule activators of SIRT1 as therapeuticsfor treatment of metabolic disorders. Using an in vitrofluorescence assay, the cancer therapeutic camptothecinincreased SIRT1 enzymatic activity by 5.5-fold, indicatingit to be a potent SIRT1 activator. Camptothecin also elevatedthe nicotinamide adenine dinucleotide (NAD)?/NADH ratio and increased SIRT1 protein levels in differentiatedC2C12 myogenic cells. Treatment of C2C12 myotubeswith camptothecin increased phosphorylation ofAMP-dependent kinase (AMPK) and acetyl-coenzyme Acarboxylase, caused nuclear translocation and deacetylationof forkhead box O1 (FoxO1), increased transcriptionand protein expression of adipose triglyceride lipase(ATGL), decreased the amount of intracellular oil droplets,and significantly increased b-oxidation of fatty acids. These in vitro data were confirmed in vivo as camptothecintreatment of C57BL/6J mice reduced fat and plasmatriglyceride levels. All of the above camptothecin-inducedalterations were attenuated by the SIRT1-specific inhibitornicotinamide and/or 6-[4-(2-piperidin-1-ylethoxy) phenyl]-3-pyridin-4-ylpyrazolo [1,5-a]pyrimidin (compound C). Thus, camptothecin activation of SIRT1 promotes lipidcatabolism through AMPK/FoxO1/ATGL signaling.

      • Analysis of Different Activation Statuses of Human Mammary Epithelial Cells from Young and Old Groups

        Feng, Chen-Chen,Chen, Li-Na,Chen, Mei-Jun,Li, Wan,Jia, Xu,Zhou, Yan-Yan,He, Wei-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

        Human mammary epithelial cells have different proliferative statuses and demonstrate a close relationship with age and cell proliferation. Research on this topic could help understand the occurrence, progression and prognosis of breast cancer. In this article, using significance analysis of a microarray algorithm, we analyzed gene expression profiles of human mammary epithelial cells of different proliferative statuses and different age groups. The results showed there were significant differences in gene expression in the same proliferation status between elderly and young groups. Three common differentially expressed genes were found to dynamically change with the proliferation status and to be closely related to tumorigenesis. We also found elderly group had less status-related differential genes from actively proliferating status to intermediate status and more statusrelated differential genes from intermediate status than the young group. Finally, functional enrichment analyses allowed evaluation of the detailed roles of these differentially-expressed genes in tumor progression.

      • Analysis of Small Fragment Deletions of the APC gene in Chinese Patients with Familial Adenomatous Polyposis, a Precancerous Condition

        Chen, Qing-Wei,Zhang, Xiao-Mei,Zhou, Jian-Nong,Zhou, Xin,Ma, Guo-Jian,Zhu, Ming,Zhang, Yuan-Ying,Yu, Jun,Feng, Ji-Feng,Chen, Sen-Qing Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.12

        Background: : Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease mainly caused by mutations of the adenomatous polyposis coli (APC) gene with almost complete penetrance. These colorectal polyps are precancerous lesions that will inevitable develop into colorectal cancer at the median age of 40-year old if total proctocolectomy is not performed. So identification of APC germline mutations has great implications for genetic counseling and management of FAP patients. In this study, we screened APC germline mutations in Chinese FAP patients, in order to find novel mutations and the APC gene germline mutation characteristics of Chinese FAP patients. Materials and Methods: The FAP patients were diagnosed by clinical manifestations, family histories, endoscope and biopsy. Then patients peripheral blood samples were collected, afterwards, genomic DNA was extracted. The mutation analysis of the APC gene was conducted by direct polymerase chain reaction (PCR) sequencing for micromutations and multiplex ligation-dependent probe amplification (MLPA) for large duplications and/or deletions. Results: We found 6 micromutations out of 14 FAP pedigrees, while there were no large duplications and/or deletions found. These germline mutations are c.5432C>T(p. Ser1811Leu), two c.3926_3930delAAAAG (p.Glu1309AspfsX4), c.3921_3924delAAAA (p.Ile1307MetfsX13), c3184_3187delCAAA(p.Gln1061AspfsX59) and c4127_4126delAT (p.Tyr1376LysfsX9), respectively, and all deletion mutations resulted in a premature stop codon. At the same time, we found c.3921_3924delAAAA and two c.3926_3930delAAAAG are located in AAAAG short tandem repeats, c3184_3187delCAAA is located in the CAAA interrupted direct repeats, and c4127_4128 del AT is located in the 5'-CCTGAACA-3', 3'-ACAAGTCC-5 palindromes (inverted repeats) of the APC gene. Furthermore, deletion mutations are mostly located at condon 1309. Conclusions: Though there were no novel mutations found as the pathogenic gene of FAP in this study, we found nucleotide sequence containing short tandem repeats and palindromes (inverted repeats), especially the 5 bp base deletion at codon 1309, are mutations in high incidence area in APC gene,.

      • Novice Corpus Users' Gains and Views on Corpus-based Lexical Development: A Case Study of COVID-19-related Expressions

        Chen, Mei-Hua Institute for Corpus Research 2021 Asia pacific journal of corpus research Vol.2 No.1

        Recently, corpus assisted vocabulary instruction has been attracting a lot of interest. Most studies have focused on understanding language learners' receptive vocabulary knowledge. Limited attention has been paid to learners' productive competence. To fill this gap, this study attended to learners' productive lexical development in terms of form, meaning and use respectively. This study introduced EFL learners to the corpus-based language pedagogy to learn COVID-19 theme-based vocabulary. To investigate the gains and views of 33 EFL first-year college students, a sentence completion task and a questionnaire were developed. Learners' productive performances in the three lexical knowledge aspects (i.e., form, meaning and use) were particularly targeted. The results revealed that the students achieved significant gains in all aspects regardless of their proficiency level. In particular, the less proficient students achieved greater knowledge retention compared with their highly proficient counterparts. Meanwhile, students showed positive attitudes towards the corpus-based approach to vocabulary learning.

      • Efficacy of Pap Test in Combination with ThinPrep Cytological Test in Screening for Cervical Cancer

        Chen, Hua,Shu, Hui-Min,Chang, Zhou-Lin,Wang, Zhi-Feng,Yao, Hai-Hong,Zhu, Hong-Mei,Lu, Tian-Mei,Ma, Qiang-Yan,Yang, Bin-Lie Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

        Background: Our aim was to investigate the efficacy of the Pap test in combination with the ThinPrep cytological test (TCT) in screening for cervical cancer in China. Design: From March 2006 to October 2008, 988 women with the mean age $46.4{\pm}10.5$ years (range, 23-80 years) were recruited to receive cervical cancer screening. Pap test results ${\geq}$ grade III and TCT findings ${\geq}$ ASCUS/AGUS were considered abnormal. Subjects with a Pap test result ${\geq}$ grade IIb received TCT. Colposcopy and biopsies were performed in all participants, and final diagnosis was based on pathological findings. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Youden index for predicting CIN I or above were determined. Results: The sensitivity, specificity, PPV, NPV and Youden index of the Pap test were 43.1%, 97.2%, 70.0%, 91.9%, and 40.3%, respectively. The same values for TCT in predicting CIN were 80.0%, 63.2%, 16.0%, 97.3%, and 43.2%, respectively. The two tests in combination gave values for predicting CIN of 64.8%, 87.6%, 43.6%, 94.4%, and 53.5%, respectively. Combined testing exhibited the highest Youden index (53.4%). Conclusion: The Pap test with a reduced threshold in combination with the TCT has high sensitivity and high specificity in screening for cervical cancer.

      • THE DETERMINANTS OF CONSUMER’S INTENTION TO CONTINUE TO USE OR APPLY FOR THE DEPARTMENT STORE CO-BRANDED CREDIT CARD

        Mei-Fang Chen,Chih-Hao Chiang 글로벌지식마케팅경영학회 2014 Global Marketing Conference Vol.2014 No.10

        Marketers commence to use types of brand alliance strategies including co-branding. Many previous studies focused on the strategic performance of the co-branded credit card or loyalty programs. The introduction of the department store co-branded credit card successfully increases revenues and expands the market shares for both the banking industry and the department store industry in Taiwan. In view of the importance of co-branding strategy to extend market share for both the banking industry and the retailing industry in Taiwan, it is worthy to have a better understanding of whether or not consumer’s affective loyalty to the bank and/or consumer’s affective loyalty to the department store will influence his/her attitude toward the department store co-branded credit card, which in turn influence his/her intention to continue to use or apply for the co-branding credit card. This study aims to ascertain what factors determine consumer’s intention to continue to use and/or to apply for the department store co-branded credit card. This study collected data on the Internet Website from December 8, 2013 to January 30, 2014. A total of 444 valid data were used in this study. The two-stage procedure of structural equation model (SEM) analysis was conducted to examine the hypothetical causal relationship in the proposed theoretical model. The results indicate that for those who had applied for the department store co-branded credit card, consumer’s affective loyalty to the bank and consumer’s affective loyalty to the department store indeed exert positive impacts on his/her attitude toward department store co-branded credit card, which in turn influence his/her intention to continue to use the co-branded credit card. In addition, for those who did not have the department store co-branded credit card, consumer’s affective loyalty to the department store can induce his/her attitude toward department store co-branded credit card, which in turn influences his/her intention to apply for co-branding credit card. The implications and suggestions for both the banking industry and the retailing industry are also provided in this study.

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