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.

Tetrazolium Violet Induced Apoptosis and Cell Cycle Arrest in Human Lung Cancer A549 Cells

( Jian Mei Lu ),( Xiao Hong Zhang ),( Nan Zhang ),( Qing Zhong Kong ),( Yun Feng Zhao ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.2

Tetrazolium violet is a tetrazolium salt and has been proposed as an antitumor agent. In this study, we reported for the fl rst time that tetrazolium violet not only inhibited human lung cancer A549 cell proliferation but also induced apoptosis and blocked cell cycle progression in the G1 phase. The results showed that tetrazolium violet signifl cantly decreased the viability of A549 cells at 5-15 M. Tetrazolium violet -induced apoptosis in A549 cells was confl rmed by H33258 staining assay. In A549, tetrazolium violet blocked the progression of the cell cycle at G1 phase by inducing p53 expression and further up-regulating p21/WAF1 expression. In addition, an enhancement in Fas/APO-1 and its two forms of ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), as well as caspase, were responsible for the apoptotic effect induced by tetrazolium violet. The conclusion of this study is that tetrazolium violet induced p53 expression which caused cell cycle arrest and apoptosis. These fl ndings suggest that tetrazolium violet has strong potential for development as an agent for treatment lung cancer.

Atom Transfer Radical Polymerization of Hexadecyl Acrylate Using CuSCN as the Catalyst

Wen Jian Xu,Xiu Lin Zhu,Zhen Ping Cheng,Jian Ying Chen,Jian Mei Lu 한국고분자학회 2004 Macromolecular Research Vol.12 No.1

OPE molecular junction as a hydrogen gas sensor

Jian-Guo Xin,Chuan-Lu Yang,Mei-Shan Wang,Xiao-Guang Ma 한국물리학회 2018 Current Applied Physics Vol.18 No.3

Oligo(phenylene ethynylene) (OPE) molecular junction has been suggested as a H2 molecule sensor based on calculations using the first principles of density–functional theory and non-equilibrium Green's function. The electronic transport properties of the OPE molecule between two Au electrodes with or without adsorbed H2 molecules are investigated. Results show that the adsorbed H2 molecule significantly changes the characteristics of the current–voltage curve of the OPE molecular junction. The pure OPE molecular junction exhibits a significant negative differential resistance, but this kind of phenomenon will disappear or weaken after hydrogen molecules are adsorbed. The conductance of the junction also obviously decreases in the bias range of [−0.4, 0.4] V after adsorbing H2 molecules. These effects can be used to design a H2 molecule sensor.

Efficacy and Safety of Endostar^® Combined with Chemotherapy in Patients with Advanced Soft Tissue Sarcomas

Zhang, Lu-Ping,Liao, Xing-Yun,Xu, Yan-Mei,Yan, Lv-Jun,Yan, Gui-Fang,Wang, Xin-Xin,Duan, Yu-Zhong,Sun, Jian-Guo Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors, and approximately 40-50% of patients with STS develop metastatic disease. The median overall survival of those patients was 12 months and their 5-year survival rate was 8%. Therefore, study on more effective treatment, especially the targeting therapies, is urgently needed. Objective: To evaluate the efficacy and safety of Endostar$^{(R)}$ combined with chemotherapy in patients with advanced STS. Methods: A retrospective case-series study was conducted in Cancer Institute of PLA, Xinqiao Hospital. A total of 71 patients suffering from advanced STS (IIB - IV) were included, of whom 49 cases treated with chemotherapy alone were defined as the control group and the rest 22 cases treated with the traditional chemotherapy combined with Endostar$^{(R)}$ were defined as the test group. The short-term therapeutic effects including objective response rate (ORR), disease control rate (DCR) and safety were evaluated in the two groups. In the follow-up, progression-free survival (PFS) and overall survival (OS) were also observed. Results: In the test and control groups, the ORR was 18.2% and 12.2%, respectively (P=0.767), and the DCR was 86.4% and 61.2%, respectively (P=0.034). The median time to progression in the test and control groups was 120 days and 70 days with significant difference (P = 0.017), while the median overall survival was 452 days and 286 days without significant difference (P=0.503). The one-year survival rate in the test group and control group was 56.2% and 35.4%, respectively, while the two-year survival rate was 30.2% and 26.5%, respectively. No significant difference in the side effects was found between the two groups. Conclusions: Endostar$^{(R)}$ combined with chemotherapy resulted in a higher DCR and longer PFS in the patients with advanced STS, and the toxicity was tolerable.

The inflammation regulation effects of Enterococcus faecium HDRsEf1 on human enterocyte-like HT-29 cells

Zhongyuan Tian,Lu Yang,Penghui Li,Yuncai Xiao,Jian Peng,Xiliang Wang,Zili Li,Mei Liu,Dingren Bi,Deshi Shi 한국통합생물학회 2016 Animal cells and systems Vol.20 No.2

Enterococcus faecium HDRsEf1 strain used as a probiotic to inhibit intestine inflammation and improve animal growth performance has been proved by our research team; however, it remains unclear how HDRsEf1 was recognized by intestine cells and how it activates the downstream pathway which benefit intestine health. In this study, HDRsEf1 was used to stimulate HT-29 cell line to partially uncover the intestine benefit mechanism of HDRsEf1. The results of cell viability assays showed that HDRsEf1 had no toxicity on HT-29 at concentrations up to 1 × 108 CFU/mL, HDRsEf1 could upregulate the TLR1, TLR2, and TLR6 mRNA level, especially TLR2, and significantly downregulate the mRNA level of TLR4, TLR5, TLR7, TLR8, but did not significantly affect the mRNA or protein level of MyD88, which suggests that HDRsEf1 activates the TLR2 pathway in an MyD88-independent pattern. HDRsEf1 could significantly downregulate the mRNA level of pro-inflammatory factors IL-1β, IL-6, IL-8, IL-12p35, IL-17, and TNF-α and did not affect the anti-inflammatory factors IL-10, PPAR-γ, and TSLP; besides HDRsEf1 did not upregulate the degradation of IκB in HT-29 cells. By contrast, enterohemorrhagic E. coli (EHEC) O157:H7 strongly up-regulated the mRNA level of pro-inflammatory factors IL-1β, IL-6, IL-8, IL-23, and TNF-α, downregulated obviously anti-inflammatory factor PPAR-ɣ, and obviously upregulated the degradation of IκB, which suggested that HDRsEf1 may act as an antagonist to regulate intestine inflammation response to intestine pathogen. These findings shed a light on the intestine benefit mechanism of HDRsEf1.

Interaction between Barium Oxide and Carbon Film in BaO/C/Mo System under High Temperature

Yue Hui Lu,Xue Mei Wu,Lan Jian Zhuge,Xiang Huai Liu 한국물리학회 2005 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.46 No.1

Carbon ¯lm, used as the coating of the Mo grid in pulsed-controlled grid traveling wave tubes, can eectively suppress electron emission from the Mo grid contaminated by the emission material of the hot cathode, i.e. BaO or Ba, so that the lifetime of the tubes can be prolonged signi¯cantly but the reasons for it have not been well understood. To study the eect of it on the BaO/Mo system under high temperature, carbon ¯lms were prepared on Mo substrate at room temperature by a dual-ion-beam sputtering deposition system, and post-annealing was conducted to know their microstructure under high temperature. In our experiments, BaO layers were coated on Mo and carbon-coated Mo substrates by the chemical method to compare with each other, and the prepared BaO/Mo and BaO/C/Mo samples were annealed at two dierent temperatures of 973 K and 1223 K in order to investigate the interaction between barium oxide and carbon ¯lm under high temperature. The results show that the BaO/C/Mo changes into C/Mo after the exhaustion of BaO at 1223 K, nevertheless, This does not happen at 973 K. In this paper, the mechanism whereby the addition of carbon ¯lm can suppress the grid emission under its operating condi-tion is discussed according to the experimental results and the calculation of the reaction free energy.

Development of High-specificity Antibodies against Renal Urate Transporters Using Genetic Immunization

( Guo Shuang Xu ),( Xiang Mei Chen ),( Di Wu ),( Suo Zhu Shi ),( Jian Zhong Wang ),( Rui Ding ),( Quan Hong ),( Zhe Feng ),( Shu Peng Lin ),( Yang Lu ) 생화학분자생물학회 2006 BMB Reports Vol.39 No.6

Significance and Application of Digital Breast Tomosynthesis for the BI-RADS Classification of Breast Cancer

Cai, Si-Qing,Yan, Jian-Xiang,Chen, Qing-Shi,Huang, Mei-Ling,Cai, Dong-Lu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Background: Full-field digital mammography (FFDM) with dense breasts has a high rate of missed diagnosis, and digital breast tomosynthesis (DBT) could reduce organization overlapping and provide more reliable images for BI-RADS classification. This study aims to explore application of COMBO (FFDM+DBT) for effect and significance of BI-RADS classification of breast cancer. Materials and Methods: In this study, we selected 832 patients who had been treated from May 2013 to November 2013. Classify FFDM and COMBO examination according to BI-RADS separately and compare the differences for glands in the image of the same patient in judgment, mass characteristics display and indirect signs. Employ Paired Wilcoxon rank sum test was used in 79 breast cancer patients to find differences between two examine methods. Results: The results indicated that COMBO pattern is able to observe more details in distribution of glands when estimating content. Paired Wilcoxon rank sum test showed that overall classification level of COMBO is higher significantly compared to FFDM to BI-RADS diagnosis and classification of breast (P<0.05). The area under FFDM ROC curve is 0.805, while that is 0.941 in COMBO pattern. COMBO shows relation of mass with the surrounding tissues, the calcification in the mass, and multiple foci clearly in breast cancer tissues. The optimal sensitivity of cut-off value in COMBO pattern is 82.9%, which is higher than that in FFDM (60%). They share the same specificity which is both 93.2%. Conclusions: Digital Breast Tomosynthesis (DBT) could be used for the BI-RADS classification in breast cancer in clinical.

Differential microRNA Expression by Solexa Sequencing in the Sera of Ovarian Cancer Patients

Ji, Ting,Zheng, Zhi-Guo,Wang, Feng-Mei,Xu, Li-Jian,Li, Lu-Feng,Cheng, Qi-Hui,Guo, Jiang-Feng,Ding, Xian-Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

MicroRNAs are a class of small noncoding RNA which play important regulatory roles in a variety of cancers. MiRNA-specific expression profiles have been reported for several pathological conditions. In this study, we combined large scale parallel Solexa sequencing to identify 11 up-regulated miRNAs and 19 down-regulated miRNAs with computational techniques in the sera of ovarian cancer patients while using healthy serum as the control. Among the above, four miRNAs (miR-22, miR-93, miR-106b, miR-451) were validated by quantitative RT-PCR and found to be significantly aberrantly expressed in the serum of ovarian cancer patients (P<0.05). There were no significant differences between samples from cancer stage I/II and III/IV. However, the levels of miR-106b (p=0.003) and miR-451 (p=0.007) were significantly different in those patients under and over 51 yearsof age. MiR-451 and miR-93 were also specific when analyzed with reference to different levels of CA125. This study shows that Solexa sequencing provides a promising method for cancer-related miRNA profiling, and selectively expressed miRNAs could be used as potential serum-based biomarkers for ovarian cancer diagnosis.