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      • KCI등재

        Realgar transforming solution-induced differentiation of NB4 cell by the degradation of PML/RARa partially through the ubiquitin–proteasome pathway

        Yang Hai,Xin Wang,Peng Song,Jian-yin Li,Longhe Zhao,Fei Xie,Xiang-min Tan,Qin-Jian Xie,Lan Yu,Yang Li,Zhengrong Wu,Hong Yu Li 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.8

        PML/retinoic acid receptor alpha (RARa), as ahallmark of acute promyeloid leukemia (APL), is directlyrelated to the outcome of clinical APL remedy. It isreported that arsenicals can effectively degrade PML/RARa, such as arsenic trioxide and realgar. However, thehigh toxicity or insolubility have hampered their clinicalapplications. Realgar transforming solution (RTS) wasproduced from realgar by bioleaching process in our lab. Previous studies demonstrated that RTS had a significantanti-cancer ability on chronic myeloid leukemia throughoncoprotein degradation. The capacity of RTS on treatingAPL is what is focused on in this study. The results showedthat RTS had a noticeable sensitivity in NB4 cell, and RTSremarkably down-regulated PML/RARa expression andinduced cell differentiation. Further, RTS could accumulatePML/RARa into the nuclear bodies and then executedegradation, which could be reversed by proteasomeinhibitor MG132. The results also exhibited that thereduction of RTS-induced PML/RARa expression accompaniedby the elevation of ubiquitin and SUMO-1 proteinexpression. Finally, PML and SUMO-1 had been demonstratedto be co-localized after RTS treatment byimmunofluorescence co-localization assay and immunoprecipitationassay. In conclusion, these results suggestedthat RTS-induced cell differentiation may attribute to thePML/RARa degradation partially through the ubiquitin–proteasome pathway.

      • SCIESCOPUSKCI등재

        Computational Prediction of Alzheimer's and Parkinson's Disease MicroRNAs in Domestic Animals

        Wang, Hai Yang,Lin, Zi Li,Yu, Xian Feng,Bao, Yuan,Cui, Xiang-Shun,Kim, Nam-Hyung Asian Australasian Association of Animal Productio 2016 Animal Bioscience Vol.29 No.6

        As the most common neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the main health concerns for the elderly population. Recently, microRNAs (miRNAs) have been used as biomarkers of infectious, genetic, and metabolic diseases in humans but they have not been well studied in domestic animals. Here we describe a computational biology study in which human AD- and PD-associated miRNAs (ADM and PDM) were utilized to predict orthologous miRNAs in the following domestic animal species: dog, cow, pig, horse, and chicken. In this study, a total of 121 and 70 published human ADM and PDM were identified, respectively. Thirty-seven miRNAs were co-regulated in AD and PD. We identified a total of 105 unrepeated human ADM and PDM that had at least one 100% identical animal homolog, among which 81 and 54 showed 100% sequence identity with 241 and 161 domestic animal miRNAs, respectively. Over 20% of the total mature horse miRNAs (92) showed perfect matches to AD/PD-associated miRNAs. Pigs, dogs, and cows have similar numbers of AD/PD-associated miRNAs (63, 62, and 59). Chickens had the least number of perfect matches (34). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that humans and dogs are relatively similar in the functional pathways of the five selected highly conserved miRNAs. Taken together, our study provides the first evidence for better understanding the miRNA-AD/PD associations in domestic animals, and provides guidance to generate domestic animal models of AD/PD to replace the current rodent models.

      • Updated Assessment of the Association of the XRCC1 Arg399Gln Polymorphism with Lung Cancer Risk in the Chinese Population

        Yang, Hai-Yan,Yang, Si-Yu,Shao, Fu-Ye,Wang, Hai-Yu,Wang, Ya-Dong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

        Background: Published studies have reported relationships between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and lung cancer risk in Chinese population. However, the epidemiological results remained controversial. The objective of this study was to clarify the association of XRCC1 Arg399Gln polymorphism with lung cancer risk in the Chinese population. Materials and Methods: Systematic searches were performed through the database of Medline/Pubmed, Web of Science, Embase, CNKI and WanFang Medical Online. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated to estimate the strength of the association. Results: Overall, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.36, 95%CI: 1.09-1.71) in the Chinese population on the basis of 19 studies with 5,416 cases and 5,782 controls. We did not observe any association between XRCC1 codon 399 Arg/Gln and Arg/Gln+Gln/Gln polymorphisms and lung cancer risk (OR=1.00, 95%CI: 0.92-1.08 and OR=1.05, 95%CI: 0.97-1.13, respectively). Limiting the analysis to studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.18, 95%CI: 1.01-1.38). When stratified by source of control, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Arg/Gln+Gln/Gln genotype on the basis of hospitalized patient-based controls (OR=1.21, 95%CI: 1.04-1.42) and among subjects carrying XRCC1 codon 399 Gln/Gln genotype on the basis of healthy subject-based controls (OR=1.22, 95%CI: 1.04-1.43). Conclusions: Our findings indicated that certain XRCC1 Arg399Gln variants might affect the susceptibility of lung cancer in Chinese population. Larger sample size studies are required to confirm our findings.

      • Increased Sister Chromatid Exchange in Peripheral Blood Lymphocytes from Humans Exposed to Pesticide: Evidence Based on a Meta-analysis

        Yang, Hai-Yan,Liu, Jing,Yang, Si-Yu,Wang, Hai-Yu,Wang, Ya-Dong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

        Background: Sister chromatid exchange (SCE) in human peripheral blood lymphocytes is one of the most extensively studied biomarkers employed to evaluate genetic damage subsequent to pesticide exposure. Objective: To estimate the pooled levels of SCE in human peripheral blood lymphocytes among population exposed to pesticide. Materials and Methods: Meta-analysis on the association between SCE frequency and pesticide exposure was performed with STATA 10.0 software package and Review Manager 5.0.24 in this study. Results: The overall means of SCE were 7.88 [95% confidence intervals (95%CI): 6.71-9.04] for exposure group and 6.05 (95%CI: 5.13-6.95) for controls, respectively. There was statistically significant difference in the SCE frequency in human peripheral blood lymphocytes between pesticide-exposed groups and control groups, and the summary estimate of weighted mean difference was 1.69 (95%CI: 1.01-2.38). We also observed that pesticide-exposed population had significantly higher SCE frequency than control groups among smokers, nonsmokers, pesticide applicator, pesticide producer, other exposure population and Asian population in stratified analyses. Conclusions: Data indicate that the SCE frequency in human peripheral blood lymphocytes might be an indicator of early genetic esffects for pesticide-exposed populations.

      • 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.

      • SCIESCOPUSKCI등재

        Chemical transformation and target preparation of saponins in stems and leaves of Panax notoginseng

        Wang, Ru-Feng,Li, Juan,Hu, Hai-Jun,Li, Jia,Yang, Ying-Bo,Yang, Li,Wang, Zheng-Tao The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.3

        Background: Notoginsenoside Ft1 is a promising potential candidate for cardiovascular and cancer disease therapy owing to its positive pharmacological activities. However, the yield of Ft1 is ultralow utilizing reported methods. Herein, an acid hydrolyzing strategy was implemented in the acquirement of rare notoginsenoside Ft1. Methods: Chemical profiles were identified by ultraperformance liquid chromatography coupled with quadruple-time-of-flight and electrospray ionization mass spectrometry (UPLC-Q/TOF-ESI-MS). The acid hydrolyzing dynamic changes of chemical compositions and the possible transformation pathways of saponins were monitored by ultrahigh-performance LC coupled with tandem MS (UHPLC-MS/ MS). Results and conclusion: Notoginsenoside Ft1 was epimerized from notoginsenoside ST4, which was generated through cleaving the carbohydrate side chains at C-20 of notoginsenosides Fa and Fc, and vinaginsenoside R7, and further converted to other compounds via hydroxylation at C-25 or hydrolysis of the carbohydrate side chains at C-3 under the acid conditions. High temperature contributed to the hydroxylation reaction at C-25 and 25% acetic acid concentration was conducive to the preparation of notoginsenoside Ft1. C-20 epimers of notoginsenoside Ft1 and ST4 were successfully separated utilizing solvent method of acetic acid solution. The theoretical preparation yield rate of notoginsenoside Ft1 was about 1.8%, which would be beneficial to further study on its bioactivities and clinical application.

      • KCI등재

        Identification and expression profiles of chitin deacetylase genes in the rice leaf folder, Cnaphalocrocis medinalis

        Hai-Zhong Yu,Ming-Hui Liu,Xue-Yang Wang,Xin Yang,Wan-Ling Wang,Lei Geng,Dong Yu,Xue-Lan Liu,Gui-Ying Liu,Jia-Ping Xu 한국응용곤충학회 2016 Journal of Asia-Pacific Entomology Vol.19 No.3

        Chitin deacetylase (CDA) is an insect chitin degradation enzyme that catalyzes the deacetylation of chitin to form chitosan. In this study, combination of rapid-amplification of cDNA ends (RACE) technology with Cnaphalocrocis medinalis transcriptome database analysis revealed the presence of at least five C. medinalis CDAs (CmCDAs), which were CmCDA1, CmCDA2, CmCDA4, CmCDA5, and CmCDA6. The cDNA sequences of CmCDA1, CmCDA2, and CmCDA4 hadwhole open reading frame (ORF) for further analysis. Phylogenetic analysis indicated that insect CDAs could be categorized into five groups. CmCDAs' structural domain analysis revealed that all three CDAs contained the chitin deacetylase-like catalytic domain. CmCDA1 and CmCDA2 belong to Group I because they both contain the chitin-binding peritrophin-A domain (ChBD), low-density lipoprotein receptor class A domain (LDLa), and chitin deacetylase-like catalytic domain. CmCDA4 only contains ChBD and chitin deacetylase-like catalytic domain thus belongs to Group III. Tissue and developmental stage expression analysis showed that the expression levels of CmCDA1, CmCDA2, and CmCDA4 are significantly higher in the head than other tissues and also significantly higher in adults than in larvae. CmCDA5 had significantly higher expression in the integument than other tissues, suggesting potential roles in the process of degradation of chitin. In contrast, CmCDA5 showed relatively high expression in larvae. In conclusion, this study analyzed the cDNA sequences of three CDA genes and determined their expression and molecular characteristics, which provided a new sequence resource and improved the development of bio-pesticides and the biological pest control and contributed to management of this important agricultural pest.

      • Increased Frequency of Micronuclei in Binucleated Lymphocytes among Occupationally Pesticide-exposed Populations: A Meta-analysis

        Yang, Hai-Yan,Feng, Ruo,Liu, Jing,Wang, Hai-Yu,Wang, Ya-Dong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

        Background: The cytokinesis-block micronucleus (CBMN) assay is a standard cytogenetic tool employed to evaluate chromosomal damage subsequent to pesticide exposure. Objectives: To evaluate the pooled levels of total micronuclei (MN) and binucleated cells with micronuclei (MNC) in 1000 binucleated lymphocytes among population occupationally exposed to pesticides and further determine the more sensitive biomarker of CBMN. Materials and Methods: A meta-analysis on the pooled levels of MN and MNC in binucleated lymphocytes among occupationally pesticide-exposed populations was conducted using STATA 10.0 software and Review Manager 5.0.24 in this study. Results: We found significant differences in frequencies of MN and MNC in 1000 binucleated lymphocytes between pesticide-exposed groups and controls, and the summary estimates of weighted mean difference were 6.82 [95% confidence interval (95% CI): 4.86-8.78] and 5.08 (95% CI: 2.93-7.23), respectively. However, when we conducted sensitivity analyses further, only the MN remained statistically different, but not the MNC, the summary estimates of weight mean difference were 2.86 (95% CI: 2.51-3.21) and 0.50 (95% CI: -0.16-1.17), respectively. We also observed pesticide-exposed subjects had significantly higher MN frequencies than controls among smokers and nonsmokers, male and female populations, and American, Asian and European countries in stratified analyses. Conclusions: The frequency of MN in peripheral blood lymphocytes might be a more sensitive indicator of early genetic effects than MNC using the CBMN assay for occupationally pesticide-exposed populations.

      • 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.

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