PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (299)
 

Clipboard (0)
None
Journals
more »
Year of Publication
more »
1.  Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations 
Wu, Chen | Wang, Zhaoming | Song, Xin | Feng, Xiao-Shan | Abnet, Christian C. | He, Jie | Hu, Nan | Zuo, Xian-Bo | Tan, Wen | Zhan, Qimin | Hu, Zhibin | He, Zhonghu | Jia, Weihua | Zhou, Yifeng | Yu, Kai | Shu, Xiao-Ou | Yuan, Jian-Min | Zheng, Wei | Zhao, Xue-Ke | Gao, She-Gan | Yuan, Zhi-Qing | Zhou, Fu-You | Fan, Zong-Min | Cui, Ji-Li | Lin, Hong-Li | Han, Xue-Na | Li, Bei | Chen, Xi | Dawsey, Sanford M. | Liao, Linda | Lee, Maxwell P. | Ding, Ti | Qiao, You-Lin | Liu, Zhihua | Liu, Yu | Yu, Dianke | Chang, Jiang | Wei, Lixuan | Gao, Yu-Tang | Koh, Woon-Puay | Xiang, Yong-Bing | Tang, Ze-Zhong | Fan, Jin-Hu | Han, Jing-Jing | Zhou, Sheng-Li | Zhang, Peng | Zhang, Dong-Yun | Yuan, Yuan | Huang, Ying | Liu, Chunling | Zhai, Kan | Qiao, Yan | Jin, Guangfu | Guo, Chuanhai | Fu, Jianhua | Miao, Xiaoping | Lu, Changdong | Yang, Haijun | Wang, Chaoyu | Wheeler, William A. | Gail, Mitchell | Yeager, Meredith | Yuenger, Jeff | Guo, Er-Tao | Li, Ai-Li | Zhang, Wei | Li, Xue-Min | Sun, Liang-Dan | Ma, Bao-Gen | Li, Yan | Tang, Sa | Peng, Xiu-Qing | Liu, Jing | Hutchinson, Amy | Jacobs, Kevin | Giffen, Carol | Burdette, Laurie | Fraumeni, Joseph F. | Shen, Hongbing | Ke, Yang | Zeng, Yixin | Wu, Tangchun | Kraft, Peter | Chung, Charles C. | Tucker, Margaret A. | Hou, Zhi-Chao | Liu, Ya-Li | Hu, Yan-Long | Liu, Yu | Wang, Li | Yuan, Guo | Chen, Li-Sha | Liu, Xiao | Ma, Teng | Meng, Hui | Sun, Li | Li, Xin-Min | Li, Xiu-Min | Ku, Jian-Wei | Zhou, Ying-Fa | Yang, Liu-Qin | Wang, Zhou | Li, Yin | Qige, Qirenwang | Yang, Wen-Jun | Lei, Guang-Yan | Chen, Long-Qi | Li, En-Min | Yuan, Ling | Yue, Wen-Bin | Wang, Ran | Wang, Lu-Wen | Fan, Xue-Ping | Zhu, Fang-Heng | Zhao, Wei-Xing | Mao, Yi-Min | Zhang, Mei | Xing, Guo-Lan | Li, Ji-Lin | Han, Min | Ren, Jing-Li | Liu, Bin | Ren, Shu-Wei | Kong, Qing-Peng | Li, Feng | Sheyhidin, Ilyar | Wei, Wu | Zhang, Yan-Rui | Feng, Chang-Wei | Wang, Jin | Yang, Yu-Hua | Hao, Hong-Zhang | Bao, Qi-De | Liu, Bao-Chi | Wu, Ai-Qun | Xie, Dong | Yang, Wan-Cai | Wang, Liang | Zhao, Xiao-Hang | Chen, Shu-Qing | Hong, Jun-Yan | Zhang, Xue-Jun | Freedman, Neal D | Goldstein, Alisa M. | Lin, Dongxin | Taylor, Philip R. | Wang, Li-Dong | Chanock, Stephen J.
Nature genetics  2014;46(9):1001-1006.
We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region.
doi:10.1038/ng.3064
PMCID: PMC4212832  PMID: 25129146
2.  Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies 
Abnet, Christian C. | Wang, Zhaoming | Song, Xin | Hu, Nan | Zhou, Fu-You | Freedman, Neal D. | Li, Xue-Min | Yu, Kai | Shu, Xiao-Ou | Yuan, Jian-Min | Zheng, Wei | Dawsey, Sanford M. | Liao, Linda M. | Lee, Maxwell P. | Ding, Ti | Qiao, You-Lin | Gao, Yu-Tang | Koh, Woon-Puay | Xiang, Yong-Bing | Tang, Ze-Zhong | Fan, Jin-Hu | Chung, Charles C. | Wang, Chaoyu | Wheeler, William | Yeager, Meredith | Yuenger, Jeff | Hutchinson, Amy | Jacobs, Kevin B. | Giffen, Carol A. | Burdett, Laurie | Fraumeni, Joseph F. | Tucker, Margaret A. | Chow, Wong-Ho | Zhao, Xue-Ke | Li, Jiang-Man | Li, Ai-Li | Sun, Liang-Dan | Wei, Wu | Li, Ji-Lin | Zhang, Peng | Li, Hong-Lei | Cui, Wen-Yan | Wang, Wei-Peng | Liu, Zhi-Cai | Yang, Xia | Fu, Wen-Jing | Cui, Ji-Li | Lin, Hong-Li | Zhu, Wen-Liang | Liu, Min | Chen, Xi | Chen, Jie | Guo, Li | Han, Jing-Jing | Zhou, Sheng-Li | Huang, Jia | Wu, Yue | Yuan, Chao | Huang, Jing | Ji, Ai-Fang | Kul, Jian-Wei | Fan, Zhong-Min | Wang, Jian-Po | Zhang, Dong-Yun | Zhang, Lian-Qun | Zhang, Wei | Chen, Yuan-Fang | Ren, Jing-Li | Li, Xiu-Min | Dong, Jin-Cheng | Xing, Guo-Lan | Guo, Zhi-Gang | Yang, Jian-Xue | Mao, Yi-Ming | Yuan, Yuan | Guo, Er-Tao | Zhang, Wei | Hou, Zhi-Chao | Liu, Jing | Li, Yan | Tang, Sa | Chang, Jia | Peng, Xiu-Qin | Han, Min | Yin, Wan-Li | Liu, Ya-Li | Hu, Yan-Long | Liu, Yu | Yang, Liu-Qin | Zhu, Fu-Guo | Yang, Xiu-Feng | Feng, Xiao-Shan | Wang, Zhou | Li, Yin | Gao, She-Gan | Liu, Hai-Lin | Yuan, Ling | Jin, Yan | Zhang, Yan-Rui | Sheyhidin, Ilyar | Li, Feng | Chen, Bao-Ping | Ren, Shu-Wei | Liu, Bin | Li, Dan | Zhang, Gao-Fu | Yue, Wen-Bin | Feng, Chang-Wei | Qige, Qirenwang | Zhao, Jian-Ting | Yang, Wen-Jun | Lei, Guang-Yan | Chen, Long-Qi | Li, En-Min | Xu, Li-Yan | Wu, Zhi-Yong | Bao, Zhi-Qin | Chen, Ji-Li | Li, Xian-Chang | Zhuang, Xiang | Zhou, Ying-Fa | Zuo, Xian-Bo | Dong, Zi-Ming | Wang, Lu-Wen | Fan, Xue-Pin | Wang, Jin | Zhou, Qi | Ma, Guo-Shun | Zhang, Qin-Xian | Liu, Hai | Jian, Xin-Ying | Lian, Sin-Yong | Wang, Jin-Sheng | Chang, Fu-Bao | Lu, Chang-Dong | Miao, Jian-Jun | Chen, Zhi-Guo | Wang, Ran | Guo, Ming | Fan, Zeng-Lin | Tao, Ping | Liu, Tai-Jing | Wei, Jin-Chang | Kong, Qing-Peng | Fan, Lei | Wang, Xian-Zeng | Gao, Fu-Sheng | Wang, Tian-Yun | Xie, Dong | Wang, Li | Chen, Shu-Qing | Yang, Wan-Cai | Hong, Jun-Yan | Wang, Liang | Qiu, Song-Liang | Goldstein, Alisa M. | Yuan, Zhi-Qing | Chanock, Stephen J. | Zhang, Xue-Jun | Taylor, Philip R. | Wang, Li-Dong
Human Molecular Genetics  2012;21(9):2132-2141.
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10−8, and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19–1.40) and P= 7.63 × 10−10. An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
doi:10.1093/hmg/dds029
PMCID: PMC3315211  PMID: 22323360
3.  Quantum dots-based double imaging combined with organic dye imaging to establish an automatic computerized method for cancer Ki67 measurement 
Scientific Reports  2016;6:20564.
As a widely used proliferative marker, Ki67 has important impacts on cancer prognosis, especially for breast cancer (BC). However, variations in analytical practice make it difficult for pathologists to manually measure Ki67 index. This study is to establish quantum dots (QDs)-based double imaging of nuclear Ki67 as red signal by QDs-655, cytoplasmic cytokeratin (CK) as yellow signal by QDs-585, and organic dye imaging of cell nucleus as blue signal by 4′,6-diamidino-2-phenylindole (DAPI), and to develop a computer-aided automatic method for Ki67 index measurement. The newly developed automatic computerized Ki67 measurement could efficiently recognize and count Ki67-positive cancer cell nuclei with red signals and cancer cell nuclei with blue signals within cancer cell cytoplasmic with yellow signals. Comparisons of computerized Ki67 index, visual Ki67 index, and marked Ki67 index for 30 patients of 90 images with Ki67 ≤ 10% (low grade), 10% < Ki67 < 50% (moderate grade), and Ki67 ≥ 50% (high grade) showed computerized Ki67 counting is better than visual Ki67 counting, especially for Ki67 low and moderate grades. Based on QDs-based double imaging and organic dye imaging on BC tissues, this study successfully developed an automatic computerized Ki67 counting method to measure Ki67 index.
doi:10.1038/srep20564
PMCID: PMC4738351  PMID: 26839163
4.  Nuclear Multidrug Resistance-Related Protein 1 Is Highly Associated with Better Prognosis of Human Mucoepidermoid Carcinoma through the Suppression of Cell Proliferation, Migration and Invasion 
PLoS ONE  2016;11(2):e0148223.
Objectives
Multidrug resistance-related protein 1 (MRP1) overexpression is a well acknowledged predictor of poor response to chemotherapy, but MRP1 also correlated to better prognosis in some reports, especially for patients not pretreated with chemotherapy. In our previous study, we found nuclear translocation of MRP1 in mucoepidermoid carcinoma (MEC) for the first time. The purpose of this study was to further investigate the function of nuclear MRP1 in MEC.
Materials and Methods
Human MEC tissue samples of 125 patients were selected and stained using immunohistochemistry. The expression level of total MRP1/nuclear MRP1 of each sample was evaluated by expression index (EI) which was scored using both qualitative and quantitative analysis. The correlations between the clinicopathologic parameters and the EI of nuclear MRP1 were analyzed using Spearman’s rank correlation analysis, respectively. The effects of RNAi-mediated downregulation of nuclear MRP1 on MEC cells were assessed using flow cytometric analysis, MTT assay, plate colony formation assay, transwell invasion assay and monolayer wound healing assay.
Results
In this study, we found the EI of nuclear MRP1 was negatively correlated to the pathologic grading (r = -0.498, P<0.01) / clinical staging (r = -0.41, P<0.01) / tumor stage (r = -0.28, P = 0.02) / nodal stage (r = -0.29, P<0.01) of MEC patients. The RNAi-mediated downregulation of nuclear MRP1 further proved that the downregulation of nuclear MRP1 could increase the cell replication, growth speed, colony formation efficiency, migration and invasion ability of MEC cells.
Conclusion
Our results suggested that nuclear MRP1 is highly associated with better prognosis of human mucoepidermoid carcinoma and further study of its function mechanism would provide clues in developing new treatment modalities of MEC.
doi:10.1371/journal.pone.0148223
PMCID: PMC4734599  PMID: 26829120
5.  ORMDL3 contributes to the risk of atherosclerosis in Chinese Han population and mediates oxidized low-density lipoprotein-induced autophagy in endothelial cells 
Scientific Reports  2015;5:17194.
ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) is a universally confirmed susceptibility gene for asthma and has recently emerged as a crucial modulator in lipid metabolism, inflammation and endoplasmic reticulum (ER) stress-the mechanisms also closely involved in atherosclerosis (AS). Here we first presented the evidence of two single nucleotide polymorphisms regulating ORMDL3 expression (rs7216389 and rs9303277) significantly associated with AS risk and the evidence of increased ORMDL3 expression in AS cases compared to controls, in Chinese Han population. Following the detection of its statistical correlation with AS, we further explored the functional relevance of ORMDL3 and hypothesized a potential role mediating autophagy as autophagy is activated upon modified lipid, inflammation and ER stress. Our results demonstrated that in endothelial cells oxidized low-density lipoprotein (ox-LDL) up-regulated ORMDL3 expression and knockdown of ORMDL3 alleviated not only ox-LDL-induced but also basal autophagy. BECN1 is essential for autophagy initiation and silencing of ORMDL3 suppressed ox-LDL-induced as well as basal BECN1 expression. In addition, deletion of ORMDL3 resulted in greater sensitivity to ox-LDL-induced cell death. Taken together, ORMDL3 might represent a causal gene mediating autophagy in endothelial cells in the pathogenesis of AS.
doi:10.1038/srep17194
PMCID: PMC4658630  PMID: 26603569
6.  Toll-Like Receptor 4 Reduces Oxidative Injury via Glutathione Activity in Sheep 
Toll-like receptor 4 (TLR4) is an important sensor of Gram-negative bacteria and can trigger activation of the innate immune system. Increased activation of TLR4 can lead to the induction of oxidative stress. Herein, the pathway whereby TLR4 affects antioxidant activity was studied. In TLR4-overexpressing sheep, TLR4 expression was found to be related to the integration copy number when monocytes were challenged with lipopolysaccharide (LPS). Consequently, production of malondialdehyde (MDA) was increased, which could increase the activation of prooxidative stress enzymes. Meanwhile, activation of an antioxidative enzyme, glutathione peroxidase (GSH-Px), was increased. Real-time PCR showed that expression of activating protein-1 (AP-1) and the antioxidative-related genes was increased. By contrast, the expression levels of superoxide dismutase 1 (SOD1) and catalase (CAT) were reduced. In transgenic sheep, glutathione (GSH) levels were dramatically reduced. Furthermore, transgenic sheep were intradermally injected with LPS in each ear. The amounts of inflammatory infiltrates were correlated with the number of TLR4 copies that were integrated in the genome. Additionally, the translation of γ-glutamylcysteine synthetase (γ-GCS) was increased. Our findings indicated that overexpression of TLR4 in sheep could ameliorate oxidative injury through GSH secretion that was induced by LPS stimulation. Furthermore, TLR4 promoted γ-GCS translation through the AP-1 pathway, which was essential for GSH synthesis.
doi:10.1155/2016/9151290
PMCID: PMC4657145  PMID: 26640618
7.  MiR-215, an activator of the CTNNBIP1/β-catenin pathway, is a marker of poor prognosis in human glioma 
Oncotarget  2015;6(28):25024-25033.
MicroRNA-215 (miR-215) promotes tumor growth in various human malignancies. However, its role has not yet been determined in human glioma. Here, we found that levels of miR-215 were higher in glioma tissues than in corresponding non-neoplastic brain tissue. High miR-215 expression was correlated with higher World Health Organization (WHO) grades and shorter overall survival. Multivariate and univariate analysis indicated that miR-215 expression was an independent prognostic factor. We also found that TGF-beta1, phosphorylated beta-catenin, alpha-SMA, and fibronectin were increased in glioma tissues. Additionally, CTNNBIP1, a direct target of miR-215, was decreased in glioma compared to adjacent normal tissue. These data indicate that miR-215 activates Wnt/β-catenin signaling by increasing β-catenin phosphorylation, α-SMA expression, and fibronectin expression. It promotes TGF-β1-induced oncogenesis by suppressing CTNNBIP1 in glioma. In summary, miR-215 is overexpressed in human glioma, is involved in TGF-β1-induced oncogenesis, and can be used as a marker of poor prognosis in glioma patients.
PMCID: PMC4694812  PMID: 26317904
miR-215; glioma; prognosis; CTNNBIP1; TGF-β1
8.  Probing the coordination properties of glutathione with transition metal ions (Cr2+,Mn2+,Fe2+,Co2+, Ni2+,Cu2+,Zn2+,Cd2+,Hg2+) by density functional theory 
Journal of Biological Physics  2014;40(4):313-323.
Complexes formed by reduced glutathione (GSH) with metal cations (Cr2+, Mn2+,Fe2+,Co2+,Ni2+,Cu2+,Zn2+,Cd2+,Hg2+) were systematically investigated by the density functional theory (DFT). The results showed that the interactions of the metal cations with GSH resulted in nine different stable complexes and many factors had an effect on the binding energy. Generally, for the same period of metal ions, the binding energies ranked in the order of Cu2+>Ni2+>Co2+>Fe2+>Cr2+>Zn2+>Mn2+; and for the same group of metal ions, the general trend of binding energies was Zn2+>Hg2+>Cd2+. Moreover, the amounts of charge transferred from S or N to transition metal cations are greater than that of O atoms. For Fe2+,Co2+,Ni2+,Cu2+,Zn2+,Cd2+ and Hg2+ complexes, the values of the Wiberg bond indices (WBIs) of M-S (M denotes metal cations) were larger than that of M-N and M-O; for Cr2+ complexes, most of the WBIs of M-O in complexes were higher than that of M-S and M-N. Furthermore, the changes in the electron configuration of the metal cations before and after chelate reaction revealed that Cu2+, Ni2+,Co2+ and Hg2+ had obvious tendencies to be reduced to Cu+,Ni+,Co+ and Hg+ during the coordination process.
Electronic supplementary material
The online version of this article (doi:10.1007/s10867-014-9350-3) contains supplementary material, which is available to authorized users.
doi:10.1007/s10867-014-9350-3
PMCID: PMC4119187  PMID: 24923419
Glutathione; Metal complex; Density functional theory NBO analysis
9.  Low-Dose Cadmium Upregulates VEGF Expression in Lung Adenocarcinoma Cells 
Cadmium (Cd) is a heavy metal and environmental toxin. Exposure to Cd has been associated with a variety of human cancers. In this study, we performed in vitro assays to examine the effects of cadmium chloride (CdCl2) on A549 cells, a human lung adenocarcinoma cell line. Cd does not affect proliferation, migration, or apoptosis of A549 cells at concentrations of 0.1–10 μM. At 0.5 and 1 μM, Cd increases the expression of vascular endothelial growth factor (VEGF) (p < 0.05, p < 0.01, respectively), but not basic fibroblast growth factor (b-FGF) in A549 cells. The conditioned media were collected from the A549 cells treated with 1 μM Cd and were co-cultured with human umbilical vein endothelial cells (HUVECs). Upon treatment with the conditioned media, the proliferation and migration of HUVECs significantly increased (p < 0.01, p < 0.05, respectively), while apoptosis remained unchanged. In addition, 1 μM Cd increases the level of hypoxia inducible factor 1-α (HIF1-α), which is a positive regulator of VEGF expression. Although low-dose Cd does not directly affect the growth of lung adenocarcinoma cells, it might facilitate the development of tumors through its pro-angiogenic effects.
doi:10.3390/ijerph120910508
PMCID: PMC4586624  PMID: 26343694
cadmium; VEGF; lung adenocarcinoma; endothelial cell; angiogenesis
10.  The prevalence, incidence, management and risks of atrial fibrillation in an elderly Chinese population: a prospective study 
Background
There is limited information on prevalent and incident atrial fibrillation in Chinese. We aimed to investigate the prevalence, incidence, management and risks of atrial fibrillation in an elderly Chinese population.
Methods
In a population—based prospective study in elderly (≥60 years) Chinese, we performed cardiovascular health examinations including a 12-lead electrocardiogram at baseline in 3,922 participants and biennially during follow-up in 2,017 participants. We collected information on vital status during the whole follow-up period.
Results
The baseline prevalence of atrial fibrillation was 2.0 % (n = 34) in 1718 men and 1.6 % (n = 36) in 2204 women. During a median 3.8 years of follow-up, the incidence rate of atrial fibrillation (n = 34) was 4.9 per 1000 person-years (95 % confidence interval [CI], 3.4–6.9). In univariate analysis, both the prevalence and incidence of atrial fibrillation were higher with age advancing (P < 0.0001) and in the presence of coronary heart disease (P ≤ 0.02). Of the 104 prevalent and incident cases of atrial fibrillation, only 1 (1.0 %) received anticoagulant therapy (warfarin). These patients with atrial fibrillation, compared with those with sinus rhythm, had significantly higher risks of all-cause (n = 261, hazard ratio [HR] 1.87, 95 % CI, 1.09–3.20, P = 0.02), cardiovascular (n = 136, HR 3.78, 95 % CI 2.17–6.58, P < 0.0001) and stroke mortality (n = 44, HR 6.31, 95 % CI 2.81–14.19, P = 0.0003).
Conclusions
Atrial fibrillation was relatively frequent in elderly Chinese, poorly managed and associated with higher risks of mortality.
doi:10.1186/s12872-015-0023-3
PMCID: PMC4427946  PMID: 25953603
Atrial fibrillation; Epidemiology; Elderly Chinese; Mortality
11.  Stathmin is a potential molecular marker and target for the treatment of gastric cancer 
Objective: This study is to investigate the expression levels of stathmin in tissues of gastric cancer, and evaluate the therapeutic effects of stathmin antisense oligodeoxynucleotide (ASODN) and/or docetaxel in human gastric cancer cells. Methods: Immunohistochemistry was performed to detect the expression levels of stathmin in gastric cancer and adjacent tissues. Stathmin ASODN was transfected into gastric cancer SGC 7901 cell lines. The cell proliferation was assessed with the MTT assay, and the inhibitory rates were calculated. RT-PCR and Western blot analysis were performed to detect the mRNA and protein expression levels of stathmin, respectively. The synergistic effects of stathmin ASODN and docetaxel were evaluated. The efficacy and clinical benefit rates of the treatment of docetaxel combined with stathmin evaluation were investigated and compared. Results: Our results showed that the expression of stathmin was elevated in gastric cancer tissues, indicating a possible association between the stathmin expression and the disease occurrence. The MTT assay and tumor growth experiment revealed that stathmin ASODN significantly inhibited the proliferation of gastric cancer cells, both in vitro and in vivo. Furthermore, stathmin ASDON enhanced the inhibitory effects of docetaxel on the proliferation of gastric cancer cells, indicating a synergistic effect for the combination treatment. Importantly, docetaxel treatment was more effective for stathmin-negative gastric cancer patients, compared with stathmin-positive patients. Conclusion: Stathmin expression provides evidence for the treatment planning for gastric cancers. Stathmin might be a potential molecular marker and target for the treatment of gastric cancer.
PMCID: PMC4483895  PMID: 26131279
Gastric cancer; treatment; stathmin; docetaxel
12.  Distribution of sialic acid receptors and experimental infections with different subtypes of influenza A viruses in Qinghai-Tibet plateau wild pika 
Virology Journal  2015;12:63.
Background
The plateau pika (Ochotona curzoniae) is a small rabbit-like mammal that lives at high altitudes in the Qinghai-Tibet plateau and is in close contact with birds. Following the outbreak of highly pathogenic avian influenza (HPAI) H5N1 during 2005 in the migratory birds of Qinghai Lake, two clades of H5N1 have been found in pikas. However, the influenza virus receptor distribution in different tissues of this animal and its susceptibility to influenza A viruses have remained unclear.
Methods
The sialic acid receptor distribution tropism in pika was investigated using fluorescent Sambucus nigra and biotinylated Maackia amurensis I and II. Furthermore, the replication of three influenza A viruses H1N1, H3N2, and H5N1 in this animal was examined by immunohistochemistry and RT-PCR. Morphological and histopathological changes caused by infection were also analyzed with hematoxylin and eosin (H & E) staining.
Results
Human influenza virus-recognizing SAα2,6Gal receptors are widely expressed in the lung, kidney, liver, spleen, duodenum, ileum, rectum, and heart, whereas avian influenza virus-recognizing SAα2,3Gal receptors are strongly expressed in the trachea and lung of pika. M1 could be detected in the lungs of pikas infected with H1N1, H3N2, and H5N1 by either immunostaining or RT-PCR, and in the brain of H5N1-infected pikas. Additionally, three subtypes of influenza A viruses were able to infect pika and caused varying degrees of pneumonia with epithelial desquamation and alveolar inflammatory cell infiltration. Slight pathological changes were observed in H1N1-infected lungs. A few small bronchi and terminal bronchioles were infiltrated by lymphocytic cells in H3N2-infected lungs. In contrast, serious lung damage, such as alveolar capillary hyperemia, edema, alveolar collapse, and lymphocytic infiltrations was observed in H5N1-infected group. Furthermore, neural system changes were present in the brains of H5N1-infected pikas.
Conclusions
SAα2,6Gal receptors are extensively present in many of the tissues and organs in wild plateau pika, whereas SA2,3Gal-linked receptors are dominant on the tracheal epithelial cells. H1N1, H3N2, and H5N1 were able to infect pika and caused different degrees of pathogenic changes in the lungs. Altogether, these results suggest that wild pika has the potential to be a host for different subtypes of influenza A viruses.
Electronic supplementary material
The online version of this article (doi:10.1186/s12985-015-0290-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s12985-015-0290-8
PMCID: PMC4409991  PMID: 25880060
Sialic acid receptors; Experimental infection; Influenza A viruses; Wild plateau pika; Pathogenic changes
13.  Associations between serum potassium and sodium levels and risk of hypertension: a community-based cohort study 
Objective
Several studies have examined the relationships between dietary potassium and sodium and hypertension, but few have evaluated the association between serum potassium or sodium and risk of incident hypertension. We therefore investigated the associations between serum potassium and sodium and risk of incident hypertension in a Chinese community-based population.
Methods
A total of 839 normotensive individuals without cardiovascular disease from the Chinese Multi-Provincial Cohort Study who took part in the baseline examination in 2007–2008 and the follow-up survey in 2012–2013 were included in this study. Odds ratios (OR) and 95% confidence intervals (95%CI) for baseline serum potassium and sodium in relation to the risk of new-onset hypertension were evaluated using multivariate logistic regression models.
Results
During five years of follow-up, 218 (26.0%) individuals progressed to hypertension. Logistic regression adjusting for multiple confounders showed that every 1 mEq/L increment in baseline serum potassium level was associated with a 75% increased risk of hypertension (OR: 1.75; 95%CI: 1.01–3.04; P = 0.04). Compared with adults with serum potassium level of 4.20–4.79 mEq/L, adults with level ≥ 4.80 mEq/L had an 84% increased risk of hypertension (OR: 1.84; 95%CI: 1.14–2.96; P = 0.01). There was no significant association between serum sodium and risk of hypertension (OR: 0.96; 95%CI: 0.89–1.04; P = 0.33).
Conclusions
Baseline serum potassium level, but not baseline serum sodium level, was positively related to the risk of incident hypertension in the Chinese population.
doi:10.11909/j.issn.1671-5411.2015.02.009
PMCID: PMC4394326  PMID: 25870614
Hypertension; Potassium; Serum; Sodium
14.  Regulation of Active DNA Demethylation by an α-Crystallin Domain Protein in Arabidopsis 
Molecular cell  2014;55(3):361-371.
SUMMARY
DNA methylation patterns are dynamically controlled by DNA methylation and active DNA demethylation, but the mechanisms of regulation of active DNA demethylation are not well understood. Through forward genetic screens for Arabidopsis mutants showing DNA hypermethylation at specific loci and increased silencing of reporter genes, we identified IDM2 (increased DNA methylation 2) as a regulator of DNA demethylation and gene silencing. IDM2 dysfunction causes DNA hypermethylation and silencing of reporter genes and some endogenous genes. These effects of idm2 mutations are similar to those of mutations in IDM1, a regulator of active DNA demethylation. IDM2 encodes an α-crystallin domain protein in the nucleus. IDM2 and IDM1 interact physically and partially colocalize at discrete subnuclear foci. IDM2 is required for the full activity of H3K18 acetylation but not H3K23 acetylation of IDM1 in planta. Our results suggest that IDM2 functions in active DNA demethylation and in antisilencing by regulating IDM1.
doi:10.1016/j.molcel.2014.06.008
PMCID: PMC4302764  PMID: 25002145
15.  High-Dose Diosgenin Reduces Bone Loss in Ovariectomized Rats via Attenuation of the RANKL/OPG Ratio 
The aim of this study was to evaluate effect of diosgenin (DG) on rats that had osteoporosis-like features induced by ovariectomy (OVX). Seventy-two six-month-old female Wistar rats were subjected to either ovariectomy (n = 60) or Sham operation (SHAM group, n = 12). Beginning at one week post-ovariectomy, the OVX rats were treated with vehicle (OVX group, n = 12), estradiol valerate (EV group, n = 12), or DG at three doses (DG-L, -M, -H group, n = 12, respectively). After a 12-week treatment, administration of EV or DG-H inhibited OVX-induced weight gain, and administration of EV or DG-H or DG-M had a significantly uterotrophic effect. Bone mineral density (BMD) and indices of bone histomorphometry of tibia were measured. Levels of protein and mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) in tibia were evaluated by immunohistochemistry and in situ hybridization. Our results show that DG at a high dose (DG-H) had a significant anti-osteoporotic effect compared to OVX control. DG-H treatment down-regulated expression of RANKL and up-regulated expression of OPG significantly in tibia from OVX rats compared to control, and thus lowered the RANKL/OPG ratio. This suggests that the anti-osteoporotic effect of DG might be associated with modulating the RANKL/OPG ratio and DG had potential to be developed as alternative therapeutic agents of osteoporosis induced by postmenopause.
doi:10.3390/ijms150917130
PMCID: PMC4200779  PMID: 25257532
diosgenin; bone loss; ovariectomized rats; osteoprotegerin; receptor activator of nuclear factor kappa-B ligand
16.  Non-Polio Enteroviruses from Acute Flaccid Paralysis Surveillance in Shandong Province, China, 1988–2013 
Scientific Reports  2014;4:6167.
Enteroviruses (EVs) are important human pathogens associated with various clinical syndromes. This study represents an overview of non-polio enteroviruses (NPEVs) isolated from acute flaccid paralysis (AFP) surveillance in Shandong Province, China from 1988 to 2013. Altogether 792 and 170 NPEV isolates were isolated from stool specimens of 9263 AFP cases and 1059 contacts, respectively. Complete VP1 sequencing and typing on all 962 isolates revealed 53 NPEV types in which echovirus (E) 6 (7.6%), E14 (7.6%), E11 (7.4%), coxsackievirus (CV) B3 (7.4%), E25 (5.6%), CVB5 (4.9%), E7 (4.5%) and EV-A71 (4.4%) were the eight most commonly reported serotypes. Distinct summer–fall seasonality was observed, with June–October accounting for 79.3% of isolation from AFP cases with known month of specimen collection. Increase of isolation of EV-A71 and CVA—the predominant pathogens for the hand, foot, and mouth disease—was observed in recent years. Sequence analysis on VP1 coding region of EV-A71 and E6 suggested Shandong strains had great genetic divergence with isolates from other countries. The results described in this study provide valuable information on the circulation and emergence of different EV types in the context of limited EV surveillance in China.
doi:10.1038/srep06167
PMCID: PMC4141246  PMID: 25145609
17.  Number of Polyploid Giant Cancer Cells and Expression of EZH2 Are Associated with VM Formation and Tumor Grade in Human Ovarian Tumor 
BioMed Research International  2014;2014:903542.
To investigate the associations among the number of polyploid giant cancer cells (PGCCs) and vasculogenic mimicry (VM), EZH2 expression, and serous ovarian tumor grade, a total of 80 paraffin-embedded serous ovarian tumor samples including 21 cases of primary carcinoma and their metastatic tumors, 26 cases of primary carcinoma without metastasis, and 12 cases of serous borderline cystadenoma were analyzed. PGCCs and VM were detected in human serous ovarian tumor. The metastatic foci of ovarian carcinoma had the highest number of PGCCs and VM. The number of PGCCs and VM increased with the grade of ovarian carcinomas. PGCCs generated erythrocytes via budding and together they formed VM. Tumor cells and cancer-associated fibroblasts were positive for EZH2 immunohistochemical staining. The tumor cells and cancer associated fibroblasts in the metastatic foci had the highest staining index of EZH2 staining. Both tumor cells and cancer-associated fibroblasts express EZH2 which then contributes to the malignant grade of serous ovarian tumor.
doi:10.1155/2014/903542
PMCID: PMC4082869  PMID: 25025074
18.  Magnetic assembly-mediated enhancement of differentiation of mouse bone marrow cells cultured on magnetic colloidal assemblies 
Scientific Reports  2014;4:5125.
Here we reported an interesting phenomenon that the field-induced assemblies of magnetic nanoparticles can promote the differentiation of primary mouse bone marrow cells into osteoblasts. The reason was thought to lie in the remnant magnetic interaction inside the assemblies which resulted from the magnetic field-directed assembly. Influence of the assemblies on the cells was realized by means of interface effect rather than the internalization effect. We fabricated a stripe-like assemblies array on the glass plate and cultured cells on this surface. We characterized the morphology of assemblies and measured the mechanic property as well as the magnetic property. The cellular differentiation was measured by staining and quantitative PCR. Finally, Fe uptake was excluded as the reason to cause the phenomenon.
doi:10.1038/srep05125
PMCID: PMC4038806  PMID: 24874764
19.  Nine New Farnesylphenols from the Basidiomycete Albatrellus Caeruleoporus 
Nine previously-unreported farnesylphenols, involving eight neogrifolin derivatives (1–8) and one grifolin analogue (9), together with three known compounds, were isolated from the fruiting bodies of the mushroom Albatrellus caeruleoporus. Their structures were elucidated as (S)-17-hydroxy-18,20-ene-neogrifolin (1), (S)-18,19-dihydroxyneogrifolin (2), (S)-9-hydroxy-10,22-ene-neogrifolin (3), (9S,10R)-6,10-epoxy-9-hydroxyneo grifolin (4), (9S,10R)-6,9-epoxy-10-hydroxyneogrifolin (5), (−)-13,14-dihydroxyneogrifolin (6), albatrelin G (7), albatrelin H (8), and one grifolin analogue, (S)-10-hydroxygrifolin (9), grifolin (10), neogrifolin (11), and albatrellin (12) by extensive spectroscopic analyses and chemical methods. Compounds 7 and 8 showed weak cytotoxic activity to cell lines HL-60, SMMC-7721, A-549, and MCF-7, in vitro.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0015-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0015-5
PMCID: PMC4004861  PMID: 24858140
Albatrellus caeruleoporus; Mushroom; Polyporaceae; Farnesylphenols
20.  Nine New Farnesylphenols from the Basidiomycete Albatrellus Caeruleoporus 
Nine previously-unreported farnesylphenols, involving eight neogrifolin derivatives (1–8) and one grifolin analogue (9), together with three known compounds, were isolated from the fruiting bodies of the mushroom Albatrellus caeruleoporus. Their structures were elucidated as (S)-17-hydroxy-18,20-ene-neogrifolin (1), (S)-18,19-dihydroxyneogrifolin (2), (S)-9-hydroxy-10,22-ene-neogrifolin (3), (9S,10R)-6,10-epoxy-9-hydroxyneo grifolin (4), (9S,10R)-6,9-epoxy-10-hydroxyneogrifolin (5), (−)-13,14-dihydroxyneogrifolin (6), albatrelin G (7), albatrelin H (8), and one grifolin analogue, (S)-10-hydroxygrifolin (9), grifolin (10), neogrifolin (11), and albatrellin (12) by extensive spectroscopic analyses and chemical methods. Compounds 7 and 8 showed weak cytotoxic activity to cell lines HL-60, SMMC-7721, A-549, and MCF-7, in vitro.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0015-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0015-5
PMCID: PMC4004861  PMID: 24858140
Albatrellus caeruleoporus; Mushroom; Polyporaceae; Farnesylphenols
21.  Chronic gastritis in China: a national multi-center survey 
BMC Gastroenterology  2014;14:21.
Background
Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear.
Methods
A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded.
Results
Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis.
Conclusions
The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy.
doi:10.1186/1471-230X-14-21
PMCID: PMC3922313  PMID: 24502423
Chronic gastritis; Endoscopy; Epidemiology
22.  Extracellular HSP70/HSP70-PCs Promote Epithelial-Mesenchymal Transition of Hepatocarcinoma Cells 
PLoS ONE  2013;8(12):e84759.
Background
Extracellular heat shock protein 70 and peptide complexes (eHSP70/HSP70-PCs) regulate a variety of biological behaviors in tumor cells. Whether eHSP70/HSP70-PCs are involved in the epithelial-mesenchymal transition (EMT) of tumor cells remains unclear.
Aims
To determine the effects of eHSP70/HSP70-PCs on EMT of hepatocarcinoma cells.
Methods
The expressions of E-cadherin, HSP70, α-smooth muscle actin protein (α-SMA) and p-p38 were detected immunohistochemically in liver cancer samples. Immunofluorescence, western blotting and real-time RT-PCR methods were used to analyze the effects of eHSP70/HSP70-PCs on the expressions of E-cadherin, α-SMA and p38/MAPK in vivo.
Results
HSP70, E-cadherin, α-SMA and p-p38 were elevated in hepatocellular carcinoma tissues. The expression of HSP70 was positively correlated with malignant differentiated liver carcinoma. The expressions of HSP70, α-SMA and p-p38 correlated with recurrence-free survival after resection. eHSP70/HSP70-PCs significantly promoted the expressions of α-SMA and p-p38 and reduced the expressions of E-cadherin in vivo. The effect was inhibited by SB203580.
Conclusion
The expressions of HSP70, E-cadherin, α-SMA and p-p38 may represent indicators of malignant potential and could discriminate the malignant degree of liver cancer. eHSP70/HSP70-PCs play an important role in the EMT of hepatocellular carcinoma via the p38/MAPK pathway.
doi:10.1371/journal.pone.0084759
PMCID: PMC3874008  PMID: 24386414
23.  Engineering stem cell niches in bioreactors 
World Journal of Stem Cells  2013;5(4):124-135.
Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “niches”, to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix (synthetic and decellularized), paracrine/autocrine signaling and physical forces (i.e., mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general, bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering.
doi:10.4252/wjsc.v5.i4.124
PMCID: PMC3812517  PMID: 24179601
Stem cell engineering; Bioreactor; Differentiation; Microenvironment; Microfluidics
24.  The Cloning and Characterization of the Enolase2 Gene of Gekko japonicus and Its Polyclonal Antibody Preparation 
The enolase2 gene is usually expressed in mature neurons and also named neuron specific enolase (NSE). In the present study, we first obtained the NSE gene cDNA sequence by using the RACE method based on the expressed sequence tag (EST) fragment from the cDNA library of Gekko japonicus and identified one transcript of about 2.2 kb in central nervous system of Gekko japonicus by Northern blotting. The open reading frame of NSE is 1305 bp, which encodes a 435 amino-acid protein. We further investigated the multi-tissue expression pattern of NSE by RT-PCR and found that the expression of NSE mRNA was very high in brain, spinal cord and low in heart, while it was not detectable in other tissues. The real-time quantitative PCR was used to investigate the time-dependent change in the expression of the NSE mRNA level after gecko spinal cord transection and found it significantly increased at one day, reaching its highest level three days post-injury and then decreasing at the seventh day of the experiment. The recombinant plasmid of pET-32a-NSE was constructed and induced to express His fused NSE protein. The purified NSE protein was used to immunize rabbits to generate polyclonal antisera. The titer of the antiserum was more than 1:65536 determined by ELISA. Western blotting showed that the prepared antibody could specifically recognize the recombinant and endogenous NSE protein. The result of immunohistochemistry revealed that positive signals were present in neurons of the brain and the spinal cord. This study provided the tools of cDNA and polyclonal antibody for studying NSE function in Gekko japonicus.
doi:10.3390/ijms14058787
PMCID: PMC3676756  PMID: 23615470
Gekko japonicus; Molecular cloning; Neuron specific enolase (NSE); polyclonal antibody
25.  Complete Genome Sequence of a Bovine Viral Diarrhea Virus 2 from Commercial Fetal Bovine Serum 
Journal of Virology  2012;86(18):10233.
We isolated a bovine viral diarrhea virus (BVDV) from commercial fetal bovine serum and designated it HLJ-10. The complete genome is 12,284 nucleotides (nt); the open reading frame is 11,694 nt, coding 3,898 amino acids. Phylogenetic analysis indicated that this strain belongs to BVDV group 2.
doi:10.1128/JVI.01581-12
PMCID: PMC3446569  PMID: 22923795

Results 1-25 (299)