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A thermodynamic study of the removal of HCI and H2S from syngas

Frontiers of Chemical Science and Engineering 2012年第1期6卷 67-83页

作者： joseph lee bo feng School of Mechanical and lvlining Engineering the University of Queensland St Lucia Qld4072 Australia

Advanced integrated-gasification combined- cycle （IGCC） and integrated-gasification fuel cell （IFGC） systems require high-temperature sorbents that are capable of removing hydrogen chloride and hydrogen sulfide from coal derived gases to very low levels. HCI and H2S are highly reactive, corrosive, and toxic gases that must be removed to meet stringent environmental regulations, to protect power generation equipment and to control the emissions of contaminants. The thermodynamic behavior of 13 sorbents for the removal of HCI and H2S under various conditions including： initial toxic gas concentra- tion （1-10000 ppm）, operating pressure （0.1-11 Mpa）, temperature （300 K-1500 K）, and the presence of H2O were investigated. The correlation between HC1 and H2S was also examined. Thermodynamic calculations were carried out for the reactions of the 113 sorbents using a FaetSage 5.2 software package based on free energy minimization. The sorbents, Na2CO3, NaHCO3, K2CO3, and CaO are capable of completely removing chlorine at high temperatures （up to -1240 K） and at high pressures. Water vapor did not have any significant effects on the dechlorination capability of the sorbents. Nine of the sorbents namely; Cu20, Na2CO3, NaHCO3, K2CO3, CaO, ZnO, MnO, FeO, and Pbo, were determined to have great potential as desulfurization sorbents. Cu2Oand ZnO had the best performance in terms of the optimum operating temperature. The addition of water vapor to the reactant gas produces a slightly detrimental effi^ct on most of the sorbents, but FeO exhibited the worst performance with a reduction in the maximum operating temperature of about 428K. The dechlorination performance of the alkali sorbents was not affected by the presence of H2S in the reactions. However, the desulfurization capability of some sorbents was greatly affected by the presence of HC1. Particularly, the performance of Cu2O was significantly reduced when HC1 was present, but the performance ofFeO improved remarkably. gather

关键词： syngas cleaning sorbent desulfurization,dechlorination

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Paeoniflorin Promotes Angiogenesis in A Vascular Insufficiency Model of Zebrafish in vivo and in Human Umbilical Vein Endothelial Cells in vitro

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Chinese Journal of Integrative Medicine 2018年第7期24卷 494-501页

作者： XIN Qi-qi YANG Bin-rui ZHOU He-feng WANG Yan YI bo-wen CONG Wei-hong lee Simon Ming-Yuen CHEN Ke-ji Clinical Medical College Beijing University of Chinese Medicine State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macao Laboratory of Cardiovascular Diseases Xiyuan Hospital China Academy of Chinese Medical Sciences Department of Pharmaceutical Preparation Xiyuan Hospital China Academy of Chinese Medical Sciences

Objective： To investigate the pro-angiogenic effects of paeoniflorin（PF） in a vascular insufficiency model of zebrafish and in human umbilical vein endothelial cells（HUVECs）. Methods： In vivo, the pro-angiogenic effects of PF were tested in a vascular insufficiency model in the Tg（fli-1：EGFP）y1 transgenic zebrafish. The 24 h post fertilization（hpf） embryos were pretreated with vascular endothelial growth factor（VEGF） receptor tyrosine kinase inhibitor Ⅱ（VRI） for 3 h to establish the vascular insufficiency model and then post-treated with PF for 24 h. The formation of intersegmental vessels（ISVs） was observed with a fluorescence microscope. The m RNA expression of fms-like tyrosine kinase-1（flt-1）, kinase insert domain receptor（kdr）, kinase insert domain receptor like（kdrl） and von Willebrand factor（v WF） were analyzed by real-time polymerase chain reaction（PCR）. In vitro, the pro-angiogenic effects of PF were observed in HUVECs in which cell proliferation, migration and tube formation were assessed. Results： PF（6.25–100 μmol/L） could rescue VRI-induced blood vessel loss in zebrafish and PF（25–100 μmol/L）, thereby restoring the m RNA expressions of flt-1, kdr, kdrl and v WF, which were down-regulated by VRI treatment. In addition, PF（0.001–0.03 μmol/L） could promote the proliferation of HUVECs while PF stimulated HUVECs migration at 1.0–10 μmol/L and tube formation at 0.3 μmol/L. Conclusion： PF could promote angiogenesis in a vascular insufficiency model of zebrafish in vivo and in HUVECs in vitro.

关键词： angiogenesis paeoniflorin zebrafish human umbilical vein endothelial cell

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Construction of recombinant human nerve growth factor beta adenovirus and evaluation of its function An in vitro and in vivo study

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Neural Regeneration Research 2010年第16期5卷 1261-1269页

作者： En-feng Gao Si-Ho Choi Mi-Ae Sung bo-Han Li Samir Jabaiti Sang Bae Yoo Sung-June Kim Soung-Min Kim Jeong Won Jahng Jong-Ho lee Department of Stomatology China-Japan Friendship Hospital Beijing 100029 China Center for Stem Cell and Regenerative Medicine Keck School of Medicine University of Sourthern Californina USA Department of Oral and Maxillofacial Surgery & Dental Research Institute Seoul National University Seoul Korea Department of Plastic and Reconstructive Surgery Jordan University Hospital Amman Jordan Department of Electrical Engineering School of Electrical and Computer Science Seoul National University Seoul Korea

Exogenous delivery of nerve growth factor （NGF） promotes neural regeneration. However, the short half-life limits delivery efficacy. Therefore, a long-term, efficient, local delivery tool or scheme is needed. The purpose of this study was to construct a functioning, recombinant, adenoviral vector carrying human NGF-β （hNGF-β） DNA, and to measure expression of the constructed vector in vitro and in vivo. rhNGF-β adenoviral vector containing full-length hNGF-β cDNA was generated by homologous recombination in Escherichia CoIL The rhNGF-β adenovirus was packaged and amplified in human embryonic kidney HEK293 cells. Transformation efficiency, expression and function of rhNGF-β adenovirus for primary Schwann cells, Schwann cell lines, human embryonic kidney HEK 293 cells, CRH myoblasts, and NIH3T3 fibroblasts were evaluated. Subsequently, expression of rhNGF-β adenovirus at the peripheral nerve of rat was also assessed. Recombinant adenoviral vector carrying hNGF-β was successfully constructed and confirmed by restriction endonuclease analysis and DNA sequence analysis. Green fluorescent protein expression was observed in 90% of rhNGF-β adenovirus-infected cells （primary Schwann cells, Schwann cell line, human embryonic kidney HEK 293 cells, CRH myoblasts, and NIH3T3 fibroblasts） compared with non-infected cells. Total mRNA isolated from rhNGF-β adenovirus-infected cells exhibited strong expression. Maximum NGF release was induced by primary cultured Schwann cells at 4 days after infection, which steadily continued for 14 days. PC-12 cells exposed to media conditioned with rhNGF-β adenovirus-infected Schwann cells exhibited increased neurite extension. In vivo experiment revealed that the injected rhNGF-β adenovirus was transfected into the cells at the injected site and promoted expression of NGF, p75NTR and brain derived neurotrophic factor at the sciatic nerve and dorsal root ganglia.

关键词： nerve growth factor Schwann cell peripheral nerve regeneration adenoviral vector HEK293 cells myoblasts fibroblasts

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p38αMAP kinase promotes asthmatic inflammation through modulation of alternatively activated macrophages

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Journal of Molecular Cell Biology 2019年第12期11卷 1095-1097页

作者： Li-Nian Huang Lei Sun Li-Ming Liu Hui-Hui Zhang Zhong-bo Liang Yan Rui Jun-feng Hu Yong Zhang John WChristman feng Qian Department of Respiration and Critical Care Medicine First Affiliated Hospital of Bengbu Medical CollegeAnhui Province Key Laboratory of Translational Cancer ResearchBengbu Medical CollegeBengbu 233004China Engineering Research Center of Cell&Therapeutic Antibody Ministry of EducationSchool of PharmacyShanghai Jiao Tong UniversityShanghai 200240China Department of Internal Medicine Section of PulmonaryCritical Careand Sleep MedicineThe Ohio State UniversityColumbusOH 43210-1252USA

Asthma is characterized by reversible airflow obstruction, bronchial hyper-reactivity, and chronic airway remodeling (Al-Muhsen et al., 2011). Pulmonary macrophages have been implicated in asthmatic inflammation (lee et al., 2015;Qian et al., 2015). The p38 mitogen-activated protein kinase (MAPK) plays an essential role in inflammation, but its role in asthma has not been determined (Kim et al., 2008). Here, our data show that macrophage-specific p38α MAPK-deficient mice displayed attenuated asthmatic inflammation in response to three allergens (dust mite, ragweed, and Aspergillus;DRA). Furthermore, we found that the protective effect was strongly associated with a reduction in the alternatively activated macrophage (AAM) polarization in vivo and in vitro. Taken together, our data indicate that p38α MAPK in macrophages contributes to AAM polarization and could be a therapeutic target for asthma.

关键词： inflammation al. asthma

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FAST Observations of an Extremely Active Episode of FRB 20201124A.Ⅱ.Energy Distribution

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Research in Astronomy and Astrophysics 2022年第12期22卷 70-80页

作者： Yong-Kun Zhang Pei Wang Yi feng Bing Zhang Di Li Chao-Wei Tsai Chen-Hui Niu Rui Luo Ju-Mei Yao Wei-Wei Zhu Jin-Lin Han Ke-Jia lee De-Jiang Zhou Jia-Rui Niu Jin-Chen Jiang Wei-Yang Wang Chun-feng Zhang Heng Xu bo-Jun Wang Jiang-Wei Xu National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Research Center for Intelligent Computing Platforms Zhejiang LaboratoryHangzhou 311100China Department of Physics and Astronomy University of NevadaLas VegasNV 89154USA Nevada Center for Astrophysics University of NevadaLas VegasNV 89154USA NAOC-UKZN Computational Astrophysics Centre University of KwaZulu-NatalDurban 4000South Africa CSIRO Space and Astronomy PO Box 76EppingNSW 1710Australia Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China Kavli Institute for Astronomy and Astrophysics Peking UniversityBeijing 100871China Department of Astronomy Peking UniversityBeijing 100871China

We report the properties of more than 800 bursts detected from the repeating fast radio burst(FRB)source FRB20201124A with the Five-hundred-meter Aperture Spherical radio Telescope(FAST)during an extremely active episode on UTC 2021 September 25–28 in a series of four *** this second paper of the series,we study the energy distribution of 881 bursts(defined as significant signals separated by dips down to the noise level)detected in the first four days of our 19 hr observational campaign spanning 17 *** event rate initially increased exponentially but the source activity stopped within 24 hr after the 4th *** detection of 542 bursts in one hour during the fourth day marked the highest event rate detected from one single FRB source so *** bursts have complex structures in the time-frequency *** find a double-peak distribution of the waiting time,which can be modeled with two log-normal functions peaking at 51.22 ms and 10.05 s,*** with the emission from a previous active episode of the source detected with FAST,the second distribution peak time is smaller,suggesting that this peak is defined by the activity level of the *** calculate the isotropic energy of the bursts using both a partial bandwidth and a full bandwidth and find that the energy distribution is not significantly *** find that an exponentially connected broken-power law function can fit the cumulative burst energy distribution well,with the lower and higher-energy indices being-1.22±0.01 and-4.27±0.23,*** a radio radiative efficiency ofη_(r)=10^(-4),the total isotropic energy of the bursts released during the four days when the source was active is already 3.9×10^(46)erg,exceeding~23%of the available magnetar dipolar magnetic *** challenges the magnetar models which invoke an inefficient radio emission(e.g.,synchrotron maser models).

关键词： (stars:)pulsars:general stars:individual(FRB 20201124A) methods:data analysis

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Chinese deserts and sand fields in Last Glacial Maximum and Holocene Optimum

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Chinese Science Bulletin 2013年第23期58卷 2775-2783页

作者： LU HuaYu YI ShuangWen XU ZhiWei ZHOU YaLi ZENG Lin ZHU FangYing feng Han DONG LiNa ZHUO HaiXin YU Kaifeng MASON joseph WANG XiaoYong CHEN YingYong LU Qi WU bo DONG ZhiBao QU JianJun WANG XunMing GUO ZhengTang School of Geographic and Oceanographic Sciences Institute for Climate and Global Change Research Nanjing University College of Tourism and Environment Shaanxi Normal University Department of Geography University of Wisconsin Madison Institute of Desertification Studies Chinese Academy of Forestry Cold and Arid Regions Environmental and Engineering Research Institute Chinese Academy of Sciences Institute of Geology and Geophysics Chinese Academy of Sciences

The Last Glacial Maximum (LGM, c. 26-16 ka) and the Holocene Optimum (HO, c. 9-5 ka) were characterized by cold-dry and warm-wet climates respectively in the recently geological Earth. How Chinese deserts and sand fields responded to these distinctive climatic changes is still not clear, however. To reconstruct environments of the deserts and sand fields during the LGM and HO is helpful to understand the forcing mechanisms of environment change in this arid region, and to test paleoclimatic modeling results. Through our long-term field and laboratory investigations, 400 optically stimulated luminescence (OSL) ages and more than 100 depositional records in the Chinese deserts and sand fields were obtained; on the basis of these data, we reconstruct spatial distributions of the deserts and sand fields during the LGM and HO. Our results show that the sand fields of Mu Us, Hunshandake, Horqin and Hulun Buir in northern and northeastern China had expanded 25%, 37%, 38% and 270%, respectively, during the LGM; the sand fields of Gonghe in the northeastern Qinghai-Tibetan Plateau had expanded 20%, and the deserts of Badain Jaran, Tengger in central northern China had expanded 39% and 29% separately during the LGM; the deserts of Taklimakan, Gurbantünggüt and Kumtag in northwestern China had expanded 10%-20% respectively, compared to their modern areas. On the other hand, all of the sand fields were nearly completely covered by vegetation during the HO; the deserts in northwestern and central northern China were reduced by around 5%-20% in area during this time. Lakes in this arid region were probably expanded during the HO but this conclusion needs more investigation. Compared with the geological distributions of deserts and sand fields, human activity has clearly changed (expanded) the area of active sand dunes at the present time. Our observations show that environmental conditions of Chinese deserts and sand fields are controlled by regional climate together with human a

关键词：沙漠环境中国北部适宜期全新世末次冰期末次盛冰期库姆塔格沙漠干旱地区

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Transcriptomic landscape regulated by the 14 types of bone morphogenetic proteins(BMPs)in lineage commitment and differentiation of mesenchymal stem cells(MSCs)

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Genes & Diseases 2019年第3期6卷 258-275页

作者： Linghuan Zhang Qing Luo Yi Shu Zongyue Zeng bo Huang Yixiao feng bo Zhang Xi Wang Yan Lei Zhenyu Ye Ling Zhao Daigui Cao Lijuan Yang Xian Chen Bin Liu William Wagstaff Russell R*Reid Hue H*Luu Rex C*Haydon Michael J*lee Jennifer Moriatis Wolf Zhou Fu Tong-Chuan He Quan Kang Stem Cell Biology and Therapy Laboratory Ministry of Education Key Laboratory of Child Development and DisordersThe Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA c Ministry of Education Key Laboratory of Diagnostic Medicine School of Laboratory MedicineChicagoIL 60637USA d The Affiliated Hospitals of Chongqing Medical University Chongqing 400016China e Department of Clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang 330006China f Key Laboratory of Orthopaedic Surgery of Gansu Province Departments of Orthopaedic Surgery and Obstetrics and GynecologyThe First and Second Hospitals of Lanzhou UniversityLanzhou 730030China g Department of General Surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215004China Department of Clinical Laboratory Medicine The Affiliated Hospital of Qingdao UniversityQingdao 266061China Department of Biology School of Life SciencesSouthwest UniversityChongqing 400715China Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and *** represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult *** least 14 BMPs have been identified in *** BMPs exert distinct but overlapping biological *** a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of ***,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully ***,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of *** clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 *** also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase ***,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,Notch and PI3K/AKT/mTOR *** the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs.

关键词： bone morphogenetic proteins(BMPs) MAP kinase signaling Mesenchymal stem cells Notch signaling PI3K/AKT/mTOR pathway Smad signaling TGFb superfamily Wnt signaling

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A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort

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Genes & Diseases 2024年第4期11卷 400-410页

作者： Han Chan Fenfen Ni bo Zhao Huimin Jiang Juanjuan Ding Li Wang Xiaowen Wang Jingjing Cui Shipin feng Xiaojie Gao Xueying Yang Huan Chi Hao lee Xuelan Chen Xiaoqin Li Jia Jiao Daoqi Wu Gaofu Zhang Mo Wang Yupeng Cun Xiongzhong Ruan Haiping Yang Qiu Li Department of Nephrology Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China Department of Nephrology Shenzhen Children's HospitalShenzhenGuangdong 518034China Department of Nephrology Kunming Children's HospitalKunming Medical UniversityKunmingYunnan 650228China Department of Nephrology Wuhan Children's HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhanHubei 430015China Department of Nephrology Chengdu Women and Children Central HospitalChengduSichuan 610073China Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Department of Nephrology John Moorhead Research LaboratoryUniversity College London Medical SchoolRoyal Free CampusUniversity College LondonLondon NW32PFUnited Kingdom

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the *** conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy ***,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for *** significant SNPs were observed between SSNSWR and SDNS/***,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through ***,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/*** study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.

关键词： Frequentrelapse Genome-wide association study Human leukocyte antigen region Steroid-sensitive nephrotic syndrome

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FAST Observations of an Extremely Active Episode of FRB 20201124A.Ⅳ.Spin Period Search

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Research in Astronomy and Astrophysics 2022年第12期22卷 99-122页

作者： Jia-Rui Niu Wei-Wei Zhu Bing Zhang Mao Yuan De-Jiang Zhou Yong-Kun Zhang Jin-Chen Jiang J.L.Han Di Li Ke-Jia lee Pei Wang Yi feng Dong-Zi Li Rui Luo Fa-Yin Wang Zi-Gao Dai Chen-Chen Miao Chen-Hui Niu Heng Xu Chun-feng Zhang Wei-Yang Wang bo-Jun Wang Jiang-Wei Xu National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Frontier in Astronomy and Astrophysics Beijing Normal UniversityBeijing 102206China Department of Physics and Astronomy University of NevadaLas VegasNV 89154USA Department of Astronomy Peking UniversityBeijing 100871China NAOC-UKZN Computational Astrophysics Centre University of KwaZulu-NatalDurban 4000South Africa Kavli Institute for Astronomy and Astrophysics Peking UniversityBeijing 100871China Research Center for Intelligent Computing Platforms Zhejiang LaboratoryHangzhou 311100China Cahill Center for Astronomy and Astrophysics MC 249-17 California Institute of TechnologyPasadena CA 91125USA CSIRO Space and Astronomy PO Box 76EppingNSW 1710Australia School of Astronomy and Space Science Nanjing UniversityNanjing 210093China Key Laboratory of Modern Astronomy and Astrophysics Nanjing UniversityMinistry of EducationNanjing 210093China Department of Astronomy University of Science and Technology of ChinaHefei 230026China

We report the properties of more than 800 bursts detected from the repeating fast radio burst(FRB)source FRB 20201124A with the Five-hundred-meter Aperture Spherical radio Telescope during an extremely active episode on UTC 2021 September 25th-28th in a series of four *** this fourth paper of the series,we present a systematic search of the spin period and linear acceleration of the source object from both 996 individual pulse peaks and the dedispersed time *** credible spin period was found from this data *** rule out the presence of significant periodicity in the range between 1 ms and 100 s with a pulse duty cycleboxcar function)and linear acceleration up to 300 m s^(-2)in each of the four one-hour observing sessions,and up to 0.6 m s^(-2)in all 4 *** searches contest theoretical scenarios involving a 1 ms–100 s isolated magnetar/pulsar with surface magnetic field10 *** also perform a periodicity search of the fine structures and identify 53 unrelated millisecond-timescale“periods”in multicomponents with the highest significance of 3.9σ.The“periods”recovered from the fine structures are neither consistent nor harmonically *** they are not likely to come from a spin *** caution against claiming spin periodicity with significance below~4σwith multi-components from one-off *** discuss the implications of our results and the possible connections between FRB multi-components and pulsar microstructures.

关键词： pulsars:general methods:observational radio continuum:general

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Identification of Global DNA Methylation Signatures in Glioblastoma-Derived Cancer Stem Cells

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Journal of Genetics and Genomics 2015年第7期42卷 355-371页

作者： Eun-Joon lee Prakash Rath Jimei Liu Dungsung Ryu Lirong Pei Satish K.Noonepalle Austin Y.Shull Qi feng N.Scott Litofsky Douglas C.Miller Douglas C.Anthony Mark D.Kirk John Laterra Libin Deng Hong-bo Xin Xinguo Wang Jeong-Hyeon Choi Huidong Shi GRU Cancer Center Georgia Regents University Department of Biology College of Art and SciencesUniversity of Missouri Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological HealthFood and Drug Administration Department of Biochemistry and Molecular Biology Georgia Regents University Division of Neurological Surgery University of Missouri School of Medicine Department of Pathology and Anatomical Sciences University of Missouri School of Medicine Department of Pathology and Laboratory Medicine Brown University and Lifespan Academic Medical Center Department of Neurology The Hugo W.Moser Research Institute at Kennedy Krieger Inc.and The Johns Hopkins University School of Medicine Institute of Translational Medicine Nanchang University David H.Murdock Research Institute Department of Biostatistics and Epidemiology Georgia Regents University

Glioblastoma （GBM） is the most common and most aggressive primary brain tumor in adults. The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one proposed mechanism leading to the resilient behavior of tumor cells and poor prognosis. In this study, we performed an in-depth analysis of the DNA methylation landscape in GBM- derived cancer stem ceils （GSCs）. Parallel comparisons of primary tumors and GSC lines derived from these tumors with normal controls （a neural stem cell （NSC） line and normal brain tissue） identified groups of hyper- and hypomethylated genes that display a trend of either increasing or decreasing methylation levels in the order of controls, primary GBMs, and their counterpart GSC lines, respectively. Interestingly, concurrent promoter hypermethylation and gene body hypomethylation were observed in a subset of genes including MGMT, AJAP1 and PTPRN2. These unique DNA methylation signatures were also found in primary GBM-derived xenograft tumors indicating that they are not tissue culture-related epigenetic changes. Integration of GSC-specific epigenetic signatures with gene expression analysis further identified candidate tumor suppressor genes that are frequently down-regulated in GBMs such as SPINT2, NEFM and PENK. Forced re-expression of SPINT2 reduced glioma cell proliferative capacity, anchorage independent growth, cell motility, and tumor sphere formation in vitro. The results from this study demonstrate that GSCs possess unique epigenetic signatures that may play important roles in the pathogenesis of GBM.

关键词： Glioblastoma Cancer stem cells DNA methylation SPINT2

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