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      • Hyperthermia Promotes Apoptosis and Suppresses Invasion in C6 Rat Glioma Cells

        Wang, Dong-Chun,Zhang, Yan,Chen, Hai-Yan,Li, Xiao-Li,Qin, Li-Juan,Li, Ya-Juan,Zhang, Hong-Yi,Wang, Shuo Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

        Gliomas are a group of heterogeneous primary central nervous system tumors. Hyperthermia has proven to be a potential therapeutic tool for cancers in the clinic. However, the molecular mechanisms of hyperthermia remain unclear. The objective of this study was to investigate the effects of hyperthermia on the invasiveness in C6 glioma cells and related molecular pathways. Here our data show hyperthermia stimulated the release of tumor necrosis factor-alpha (TNF-${\alpha}$) and decreased C6 glioma cell migration and invasive capability at 30, 60, 120 and 180 min; with increased spontaneous apoptosis in C6 glioma cells at 120 min. We also found mitogen-activated protein kinase (P38 MAPK) protein expression to be increased and nuclear factor-kappa B (NF-${\kappa}B$) protein expression decreased. Based on the results, we conclude that hyperthermia alone reduced invasion of C6 glioma cells through stimulating TNF-${\alpha}$ signaling to activate apoptosis, enhancing P38 MAPK expression and inhibiting the NF-${\kappa}B$ pathway, a first report in C6 rat glioma cells.

      • KCI등재

        Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing

        Hai-Yun Wang,Ling Deng,Ying-Qing Li,Xiao Zhang,Ya-Kang Long,Xu Zhang,Yan-Fen Feng,Yuan He,Tao Tang,Xin-Hua Yang,Fang Wang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.4

        Purpose Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. Materials and Methods TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. Results The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was eight and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR–positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. Conclusion Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR–positive status could be a significant biomarker for predicting ICI response in patients.

      • KCI등재

        Tunicamycin enhances TRAIL-induced apoptosis by inhibition of cyclin D1 and the subsequent downregulation of survivin

        Hai-Yan Zhang,Zhen-Xian Du,Bao-Qin Liu,Yan-Yan Gao,Xin Meng,Yifu Guan,Wei-Wei Deng,Hua-Qin Wang 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.5

        TNF-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising cancer therapy that preferentially induces apoptosis in cancer cells, but not most normal tissues. However, many cancers are resistant to TRAIL by mechanisms that are poorly understood. In this study, we showed that tunicamycin, a naturally occurring antibiotic, was a potent enhancer of TRAIL-induced apoptosis through downregulation of survivin. The tunicamycin-mediated sensitization to TRAIL was efficiently reduced by forced expression of survivin, suggesting that the sensitization was mediated at least in part through inhibition of survivin expression. Tunicamycin also repressed expression of cyclin D1, a cell cycle regulator commonly overexpressed in thyroid carcinoma. Furthermore, silencing cyclin D1 by RNA interference reduced survivin expression and sensitized thyroid cancer cells to TRAIL; in contrast, forced expression of cyclin D1 attenuated tunicamycin-potentiated TRAIL-induced apoptosis via over-riding downregulation of survivin. Collectively, our results demonstrated that tunicamycin promoted TRAIL-induced apoptosis, at least in part, by inhibiting the expression of cyclin D1 and subsequent survivin. Of note, tunicamycin did not sensitize the differentiated thyroid epithelial cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may offer an attractive strategy for safely treating resistant thyroid cancers. TNF-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising cancer therapy that preferentially induces apoptosis in cancer cells, but not most normal tissues. However, many cancers are resistant to TRAIL by mechanisms that are poorly understood. In this study, we showed that tunicamycin, a naturally occurring antibiotic, was a potent enhancer of TRAIL-induced apoptosis through downregulation of survivin. The tunicamycin-mediated sensitization to TRAIL was efficiently reduced by forced expression of survivin, suggesting that the sensitization was mediated at least in part through inhibition of survivin expression. Tunicamycin also repressed expression of cyclin D1, a cell cycle regulator commonly overexpressed in thyroid carcinoma. Furthermore, silencing cyclin D1 by RNA interference reduced survivin expression and sensitized thyroid cancer cells to TRAIL; in contrast, forced expression of cyclin D1 attenuated tunicamycin-potentiated TRAIL-induced apoptosis via over-riding downregulation of survivin. Collectively, our results demonstrated that tunicamycin promoted TRAIL-induced apoptosis, at least in part, by inhibiting the expression of cyclin D1 and subsequent survivin. Of note, tunicamycin did not sensitize the differentiated thyroid epithelial cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may offer an attractive strategy for safely treating resistant thyroid cancers.

      • KCI등재

        Evaluation of reference genes for miRNA expression analysis in Galeruca daurica (Coleoptera: Chrysomelidae) using qRT‐PCR

        Hai-Chao WANG,Ling LI,Yan-Yan LI,Yao TAN,Bao-Ping PANG 한국곤충학회 2021 Entomological Research Vol.51 No.8

        The selection of suitable reference genes (RGs) for data normalization is a crucial step for obtaining reliable results from gene expression analysis using the quantitative real-time polymerase chain reaction (qRT-PCR). Expression stability of eleven putative RGs (miR-100-5p, miR-92a-3p, miR-998-3p, miR-279d-3p, miR-305-5p, miR-276a-3p, miR-275-3p, miR-9a-5p, miR-2a-3p, U6 snRNA and 5S rRNA) was assessed by using a web-based tool: RefFinder, which integrates four algorithms (Delta Ct, geNorm, NormFinder, and BestKeeper), and the best combination number of RGs was calculated by geNorm. Validation of selected RGs was performed by an expression analysis of let-7-5p under different experimental conditions. The best combinations of RGs were shown as follows: miR-100-5p + miR-275-3p for temperature treatment, miR-100-5p + miR-305-5p for adult tissues, miR- 276a-3p + miR-9a-5p for genders, miR-2a-3p + miR-276a-3p for days after eclosion, U6 snRNA + miR-9a-5p + miR-2a-3p for developmental stages, and U6 snRNA + miR-279d-3p for all above conditions, and there was no one RG suitable for all experimental conditions. Incorrect RG selection affected the evaluation of let-7-5p abundance. Our findings demonstrate that an integrated approach of multiple algorithms is necessary to identify reliable, stable RGs for miRNA evaluation, and provide a basis for further studies on expression and function analysis of miRNAs and their target genes in Galeruca daurica, a new pest with great outbreaks in Inner Mongolia since 2009.

      • KCI등재
      • Updated Meta-analysis of the Association Between CYP2E1 RsaI/PstI Polymorphisms and Lung Cancer Risk in Chinese Population

        Wang, Ya-Dong,Yang, Hai-Yan,Liu, Jing,Wang, Hai-Yu Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

        Background: A number of studies have reported relationships of CYP2E1 RsaI/PstI polymorphisms with susceptibility to lung cancer in Chinese population. However, the epidemiologic results have been conflictive rather than conclusive. The purpose of this study was to address the associations of CYP2E1 RsaI/PstI polymorphisms with lung cancer risk in Chinese population comprehensively. Materials and Methods: Systematic searches were conducted in the PubMed, Science Direct, Elsevier, CNKI and Chinese Biomedical Literature Databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of association. Results: Overall, we observed a decreased lung cancer risk among subjects carrying CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 genotypes (OR=0.76, 95%CI: 0.64-0.90 and OR=0.78, 95%CI: 0.66-0.93, respectively), as compared with subjects carrying the c1/c1 genotype. In subgroup analysis, we observed a decreased lung cancer risk among c1/c2 carriers in hospital-based studies (OR=0.81, 95%CI: 0.68-0.98) and among carriers with c1/c2 and c1/c2+c2/c2 genotypes in population-based studies(OR=0.57, 95%CI: 0.42-0.79 and OR=0.58, 95%CI: 0.43-0.79, respectively), as compared with subjects carrying the c1/c1 genotype. Limiting the analysis to studies with controls in Hardy-Weinberg equilibrium (HWE), we similarly observed a decreased lung cancer risk among c1/c2 and c1/c2+c2/c2 carriers (OR=0.73, 95%CI: 0.60-0.88 and OR=0.73, 95%CI: 0.60-0.88, respectively), as compared with c1/c1. Conclusions: Our results suggested that CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 variants might be a protective factor for developing lung cancer in Chinese population. Further well-designed studies with larger sample size are required to verify our findings.

      • KCI등재
      • SCIESCOPUSKCI등재

        Enhanced (R)-2-(4-Hydroxyphenoxy)Propionic Acid Production by Beauveria bassiana: Optimization of Culture Medium and H<sub>2</sub>O<sub>2</sub> Supplement under Static Cultivation

        ( Hai-feng Hu ),( Hai-yan Zhou ),( Xian-lin Wang ),( Yuan-shan Wang ),( Ya-ping Xue ),( Yu-guo Zheng ) 한국미생물 · 생명공학회 2020 Journal of microbiology and biotechnology Vol.30 No.8

        (R)-2-(4-hydroxyphenoxy)propionic acid (HPOPA) is a key intermediate for the preparation of aryloxyphenoxypropionic acid herbicides (R-isomer). In order to improve the HPOPA production from the substrate (R)-2-phenoxypropionic acid (POPA) with Beauveria bassiana CCN-A7, static cultivation and H<sub>2</sub>O<sub>2</sub> addition were attempted and found to be conducive to the task at hand. This is the first report on HPOPA production under static cultivation and reactive oxygen species (ROS) induction. On this premise, the cultivation conditions and fermentation medium compositions were optimized. As a result, the optimal carbon source, organic nitrogen source, and inorganic nitrogen source were determined to be glucose, peptone, and ammonium sulfate, respectively. The optimal inoculum size and fermentation temperature were 13.3% and 28℃, respectively. The significant factors including glucose, peptone, and H<sub>2</sub>O<sub>2</sub>, identified based on Plackett-Burman design, were further optimized through Central Composite Design (CCD). The optimal concentrations were as follows: glucose 38.81 g/l, peptone 7.28 g/l, and H<sub>2</sub>O<sub>2</sub> 1.08 g/l/100 ml. Under the optimized conditions, HPOPA titer was improved from 9.60 g/l to 19.53 g/l, representing an increase of 2.03- fold. The results obtained in this work will provide novel strategies for improving the biosynthesis of hydroxy aromatics.

      • KCI등재

        유니버설 디자인 개념을 융합한 도시의 생활가로 공간 환경 평가지표 연구 -중국 한단시를 중심으로-

        왕해연(Wang, Hai Yan),왕석(Wang Shuo),박재철(Park, Jae Chul) 한국전시산업융합연구원 2021 한국과학예술융합학회 Vol.39 No.5

        본 연구는 중국의 인구 노령화 심화, 보행자의 욕구를 소홀한 가로 건설, 유니버설 디자인 보급률 저하와 무장애시설 미비 등의 배경에서 시작되었다. 본 연구의 목적은 한단시 생활가로의 갱신 설계와 건설관리를 지도하고, 모두에게 매력적이며 안전하고 포용성 있는 양호한 생활 체험이 가능한 가로공간환경을 조성하는데 기여하기 위한 것이다. 따라서 본 논문에서 도시가로는 모두가 편리하게 이용할 수 있는 공공 공간으로 건설되어야 한다는 관점에서 모든 이용자를 배려한 장애가 없고 편안하고 살기 좋은 생활가로공간 환경의 개선 방향을 제시하기 위하여 시도하였다. 연구결과 및 내용은 다음과 같다. 첫째, 문헌 조사와 퍼지 델파이법을 활용하여 유니버설 디자인에 기초한 도시 생활가로 공간 환경 평가체계를 3개 측면 26개 지표로 구축하였다. 둘째, 인자분석 결과 일반인과 장애인은 모두 생활가로의 안전성을 가장 중요한 요인으로 여기는 것으로 나타났다. 그러나 일반인은 생활가로의 쾌적성에 더 많은 관심을 기울이고, 장애인은 가로의 포용성에 더 많은 관심을 두는 것으로 나타났다. 5개 지표의 중요성에 대한 일반인과 장애인의 인식은 현저한 차이를 보였다. 셋째, 분산 분석 결과 시각장애인, 청각/언어장애인 및 지체장애인의 생활가로 공간의 포용성의 중요성에 대한 인식은 확연한 차이를 보였다. 6개 지표의 중요성에 대한 시각장애인, 청력/언어장애인과 지체장애인의 차이는 현저하였다. 이러한 연구결과를 바탕으로 전 생애주기의 집단별(영유아 양육자, 아동, 초등학생, 건강한 일반인, 노인)생활가로 공간환경 요소에 대한 중요도와 만족도를 조사하고 연구하고, 모두에게 적용될 수 있는 한단시 생활가로 유니버설 디자인 세칙을 제정하여 생활가로를 소속감 있는 공공 공간으로 조성하여 도시민의 아름다운 삶에 대한 동경을 충족시키는데 기여해야 할 것으로 사료된다. This study started under the background of escalation of aging of population, ignoring pedestrian needs in street construction, low penetration rate of universal design and incomplete barrier-free facilities in China. The purpose of this study is to guide the renewal design and construction management of the living streets in Handan City, and to create the street space environment that is attractive, safe, and inclusive for everyone. Therefore, this paper, from the perspective that urban streets should be built into a public space that can be easily used by everyone, attempts to put forward the direction of improving the space environment of barrier-free, comfortable, and livable living streets that take care of all users. The following is the results and contents of this study: Firstly, this study, based on literature investigation and research, has constructed an evaluation system of city living streets via fuzzy Delphi method. This evaluation system includes 26 indicators in 3 aspects. Secondly, the results of factor analysis showed that both the ordinary persons and the disabled think that the safety of living streets is the most important factor. In addition, ordinary persons pay more attention to the comfort of living streets, while the disabled pay more attention to the inclusiveness of streets. There are significant differences between ordinary persons and the disabled in their cognition of the importance of the five indicators. Thirdly, the results of analysis of variance showed that there are obvious differences in the cognition of the importance of street space inclusiveness among the visually-impaired, the speaking/hearing-impaired and the physically impaired. There are significant differences in the cognition of the importance of the six indicators among the three types of disabled persons. Based on these study results, Looking forward to further investigating the emphasis and satisfaction of different types of groups (baby caregivers, children, primary school students, healthy ordinary people, the elderly) in the life cycle on the space environment elements of living streets, formulate universal design rules of living streets of Handan City for everyone, turn the living streets into a public space with a sense of belonging, and make contributions to satisfying the yearning of urban residents for a better life.

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