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Establishment and characterization of two new human embryonic stem cell lines,SYSU-1 and SYSU-2

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Donghyun Park Andy Peng Xiang Frank Fuxiang Mao Noah Walton bruce t.lahn Howard Hughes Medical Institute Department of Human GeneticsUniversity of ChicagoChicago IL 60637USA Center for Stem Cell Biology and tissue Engineering Sun Yat-sen University

＜正＞the intermediate filament protein,nestin,is a widely employed marker of multipotent neural stem/progenitor cells（NSCs）.Recent in vitro studies have implicated nestin in a number of cellular processes,but there is no evidence yet on its in vivo ***,we report the construction and functional characterization of Nestin knockout *** found mat these mice show embryonic lethality,with neuroepithelia of the developing neural tube exhibiting significantly increased *** with this in vivo observation,NSC cultures derived from knockout embryos show dramatically elevated apoptosis but no defects in proliferation or ***,nestin deficiency has no deflectable effect on the integrity of the ***,the knockout of vimentin,while abolishing nestin’s ability to polymerize into intermediate filaments in NSCs,does not lead to any apoptotic *** data demonstrate that nestin is a critical prosurvival factor in NSCs,and that nestin’s prosurvival function is surprisingly uncoupled from its structural involvement in the cytoskeleton.

关键词： nestin intermediate filament apoptosis neural stem cells neural progenitor cells vimentin

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Chinese Medical Journal 2007年第7期120卷 589-594页

作者： HUANG Guo LI Wei-qiang CHEN Rui CHEN Zhen-guang ZHANG Xiu-ming MAO Fu-xiang HUANG Shao-liang LI Shu-nong bruce t lahn Andy Peng Xiang Centre for Stem Cell Biology and tissue Engineering Sun Yat-sen University Guangzhou 510080 China Fourth People＇s Hospital of Shenzhen Shenzhen 518033 China Department of thoracic Surgery First Affiliated Hospital Sun Yat-sen University Guangzhou 510080 China

Background Human embryonic stem cells can propagate indefinitely in vitro and are able to differentiate into derivatives of all three embryonic germ layers. the excitement surrounding human embryonic stem cells lies largely in their potential to produce specialized cells that can be used for transplant therapies. However, further investigation requires additional cell lines with varying genetic background. therefore, efforts to derive and establish more human embryonic stern cell lines are highly warranted. Methods Surplus embryos （blastocysts） from donors were used to isolate the inner cell mass by immunosurgery. All cells were cultured continuously on irradiated murine embryonic fibroblasts feed layer and likely human embryonic stem cell colonies were subsequently characterized by cell surface marker staining, karyotyping and teratoma formation. Results two human embryonic stern cell lines （SYSU-1 and SYSU-2） were established from surplus embryos. the two lines express several pluripotency markers including alkaline phosphatase, SSEA- 4, tra-1-60, Oct-4, Nanog and Rex-1. they remain in undifferentiated state with normal karyotype after prolonged passages and can form embryoid bodies in vitro and teratoma in vivo. Conclusion two new human embryonic stem cell lines have been established from surplus embryos. they can be used to understand selfrenewal and differentiating mechanisms and provide more choices for regenerative medicine.

关键词： embryonic stem cells blastocysts inner cell mass cell differentiation

Assessment of embryotoxicity of compounds in cosmetics by the embryonic stem cell test

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Assessment of embryotoxicity of compounds in cosmetics by th...

Wind farm potential is higher in prime habitat for uncommon soil crust lichens

第九届中国实验动物科学年会（2010新疆）

作者： Rui Chen1,2,Jing Chen1,2,Shujun Cheng3,Jie Qinl,2,Weiqiang Lil,2,Lirong Zhang4,Hong Jiao3, Xinbing Yu1,2,Xiuming Zhang1,2,bruce t.lahn1,2,and Andy Peng Xiang1,2 1 Center for Stem Cell Biology and tissue Engineering,Sun Yat-sen University,74# Zhongshan Road 2, Guangzhou, Guangdong.PR China 510080,2the Key Laboratory for Stem Cells and tissue Engineering,Ministry of Education, Guangzhou 510080,PR China,3 Food Lab of Guangdong Entry-Exit Inspection and Quarantine technology Center. Guangzhou 510623,PR China,and 4Department of Pathophysiology,Guangdong College of Pharmacy, Guangzhou 510006,PR China

Objective the new EU legislations for cosmetics(Seventh Amendment) have laid down deadlines for the replacement of animal tests in *** policy stimulates the acceptance of in vitro approaches to test embryotoxic potentials of compounds in cosmetics *** embryonic stem cell test(ESt) designed by the European Centre for the Validation of Alternative Methods(ECVAM) is currently the most promising in vitro assay to predict the embryotoxic potential of *** this study,six selected compounds(hydroquinone,eugenol,dibutyl phthalate,antimony(Ⅲ) oxide,neodymium(Ⅲ) nitrate hydrate,melamine) formerly involved in cosmetic products were selected to test their embryotoxic potentials by the ESt.5-Fluorouracil and penicillin G were separately set as positive and negative *** embryotoxic potential was determined by the prediction model(PM),which was calculated from three endpoints,the IC50 3t3,IC50 ES,and ***,eugenol,and antimony(Ⅲ) oxide indicated with strong embryotoxicity,while dibutyl phthalate,neodymium(Ⅲ) nitrate hydrate,and melamine exhibited a weak *** results may provide a valuable attempt to expand the application of ESt to the cosmetics field.

关键词： Cosmetics embryotoxicity embryonic stem cell test

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Ecological Processes 2013年第1期2卷 108-115页

作者： Heather t Root Myrica McCune bruce McCune Department of Botany and Plant Pathology Oregon State University2082 Cordley HallCorvallisOR 97330USA Institute for Natural Resources Oregon State University210 Strand Agricultural HallCorvallisOR97331USA Department of Forest Ecosystems and Society Oregon State University321 Richardson HallCorvallisOR97331USA

Introduction:Biotic soil crust communities contribute valuable ecosystem services and biodiversity in steppe *** uncommon crust lichens Acarospora schleicheri,Fuscopannaria cyanolepra,Rhizocarpon diploschistidina,and texosporium sancti-jacobi are associated with fine-textured soils along rivers of the Columbia *** and *** indicate late-successional habitat and may serve as indicators for other rare or cryptic species associated with similar *** of the most favorable habitat for these species has been lost to urban and agricultural *** sought to overlay favorable habitats with wind farm development potential to assess whether these species are likely to be affected by renewable energy ***:We overlaid habitat models for four lichen species on land use and wind farm potential *** a sample of 5,000 points,we determined whether there were differences in probability of occurrence among wind farm potential classes within developed and natural lands using Multi-Response Permutation *** with modeled probability of occurrence greater than 60%were considered“favorable”habitats;for these,aχ2 test allowed us to determine whether favorable habitats were associated with wind farm potential ***:Sites that are developed for agriculture or have higher wind farm potential coincide with more favorable habitats for uncommon soil crust *** the favorable habitats for the four focal lichens,28–42%are already affected by development or agriculture;5–14%of favorable habitats remain in natural vegetation and are considered sites with fair or good potential for wind ***:Development of wind energy has the potential to negatively impact uncommon soil crust lichen species because favorable sites coincide with especially good habitat for these ***,as these renewable energy resources are developed,we have the opportunity to ensure that valuable soil crus

关键词： Acarospora schleicheri Agriculture Biotic soil crust Columbia river Fuscopannaria cyanolepra Land use Rhizocarpon diploschistidina Steppe texosporium sancti-jacobi

targeting t regulatory(t_(reg))cells in immunotherapy-resistant cancers

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Cancer Drug Resistance 2024年第1期7卷 1053-1077页

作者： Pavlina Spiliopoulou Paramjit Kaur tracey Hammett Giusy Di Conza Michael lahn Department of Drug Development Program Phase I UnitBeatson West of Scotland Cancer CenterGlasgow G120YNUK School of Cancer Sciences University of GlasgowGlasgow G611BDUK Department of Oncology Clinical Development iOnctura SAGeneva 1202Switzerland

Primary or secondary(i.e.,acquired)resistance is a common occurrence in cancer patients and is often associated with high numbers of t regulatory(t_(reg))cells(CD4^(+)CD25^(+)FOXP3^(+)).the approval of ipilimumab and the development of similar pharmacological agents targeting cell surface proteins on t_(reg)cells demonstrates that such intervention may overcome resistance in cancer ***,the clinical development and subsequent approval of Cytotoxic t Lymphocyte Antigen-4(CtLA-4)targeting agents can serve as a prototype for similar *** new agents aspire to be highly specific and have a reduced toxicity profile while increasing effector t cell function or effector t/t regulatory(t_(eff)/t_(reg))*** clinical development with large molecules has shown the greatest advancement,small molecule inhibitors that target immunomodulation are increasingly entering early clinical *** new small molecule inhibitors often target specific intracellular signaling pathways[e.g.,phosphoinositide-3-kinase delta(PI3K-δ)]that play an important role in regulating the function of t_(reg)*** review will summarize the lessons currently applied to develop novel clinical agents that target t_(reg)cells.

关键词： Primary and secondary resistance t regulatory cells flow cytometry mass cytometry hyperprogression

Prophylaxis with intraocular pressure lowering medication and glaucomatous progression in patients receiving intravitreal anti-VEGF therapy

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International Journal of Ophthalmology(English edition) 2022年第10期15卷 1611-1618页

作者： Jeanette Du James t Patrie Xiao-Yu Cai bruce E Prum Yevgeniy Shildkrot New York Eye and Ear Infirmary of Mount Sinai 310 East 14 StreetNew YorkNY 10003USA Department of Public Health Sciences University of VirginiaP.0.Box 800717CharlottesvilleVirginia 22908USA Department of Ophthalmology University of Virginia School of Medicine1300 Jefferson Park AveCharlottesvilleVirginia 22908USA

AIM: to investigate whether pretreatment with pressurelowering medication prior to anti-vascular endothelial factor(VEGF) injections had an effect on glaucomatous progression in patients with preexisting glaucoma or ocular hypertension(OHt).MEtHODS: A total of 66 eyes from 54 patients with a preexisting diagnosis of glaucoma or OHt, treated with six or more anti-VEGF injections were selected for chart review. Primary outcome measures were rate of visual field loss in d B/year, rate of change in retinal nerve fiber layer(RNFL) thickness in microns/year, and need for additional glaucoma ***: the number of eyes requiring additional glaucoma medication was 5 of 20(25.0%) and 14 of 46(30.4%) for the pretreated and non-pretreated groups, respectively. the number of eyes requiring glaucoma laser or surgery was 4 of 20(20.0%) and 13 of 46(28.3%) for the pretreated and non-pretreated groups, respectively. Estimated mean rate of pattern standard deviation decline was not significant in either group(P>0.073), with no difference between groups(P=0.332). Although both groups showed significant RNFL change from baseline(Ptected between groups(P=0.467).CONCLUSION: Pretreatment has no detectable effect on structural or functional glaucomatous progression. Patients receiving repeated injections may be at risk for glaucomatous complications requiring invasive intervention.

关键词： anti-vascular endothelial growth factor therapy pretreatment glaucomatous progression

Contemporary,national patterns of surgery after preoperative therapy for stageⅡ/Ⅲrectal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2022年第6期14卷 1148-1161页

作者： Celine Soriano Henry t Bahnson Jennifer A Kaplan bruce Lin Ravi Moonka Huong t Pham Hagen F Kennecke Vlad Simianu Department of Surgery Virginia Mason Franciscan HealthSeattleWA 98101United States Benaroya Research Institute SeattleWA 98101United States Department of Hematology Oncology Virginia Mason Franciscan HealthSeattleWA 98101United States Department of Radiation Oncology Virginia Mason Franciscan HealthSeattleWA 98101United States Department of Medical Oncology Providence Cancer InstititutePortlandOR 97213United States Section of Colon and Rectal Surgery Department of SurgeryVirginia Mason Medical CenterSeattleWA 98101United States

BACKGROUND Contemporary treatment of stageⅡ/Ⅲrectal cancer combines chemotherapy,chemoradiation,and surgery,though the sequence of surgery with neoadjuvant treatments and benefits of minimally-invasive surgery(MIS)is *** to describe patterns of surgical approach for stageⅡ/Ⅲrectal cancer in relation to neoadjuvant *** A retrospective cohort was created using the National Cancer *** outcome was rate of sphincter-sparing surgery after neoadjuvant *** outcomes were surgical approach(open,laparoscopic,or robotic),surgical quality(R0 resection and 12+lymph nodes),and overall *** A total of 38927 patients with clinical stageⅡorⅢrectal adenocarcinoma underwent surgical resection from *** stageⅡpatients had neoadjuvant chemoradiation less frequently compared to stageⅢ(75.8%vs 84.7%,Pt had similar rates of total neoadjuvant therapy(tNt)(27.0%vs 27.2%,P=0.697).Overall rates of total mesorectal excision without sphincter preservation were similar between clinical stageⅡandⅢ(30.0%vs 30.3%)and similar if preoperative treatment was chemoradiation(31.3%)or tNt(30.2%).Over the study period,proportion of cases approached laparoscopically increased from 24.9%to 32.5%and robotically 5.6%to 30.7%(Pthis cohort showed improved survival for MIS approaches compared to open surgery(laparoscopy HR 0.85,95%CI 0.78-0.93,and robotic HR 0.82,95%CI 0.73-0.92).CONCLUSION Sphincter preservation rates are similar across stageⅡandⅢrectal cancer,regardless of delivery of preoperative chemotherapy,chemoradiation,or *** a national level,there is a shift to predominantly MIS approaches for rectal cancer,regardless of whether sphincter sparing procedure is performed.

关键词： Rectal cancer total neoadjuvant therapy Colorectal surgery Minimally-invasive surgery Chemotherapy Radiation

Physiology of in-situ arterial revascularization in coronary artery bypass grafting: Preoperative,intraoperative and postoperative factors and influences

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World Journal of Cardiology 2016年第11期8卷 623-637页

作者： t bruce Ferguson Jr CV Sciences East Carolina Heart InstituteEast Carolina Diabetes and Obesity InstituteBrody School of Medicine at East Carolina University

Surgical revascularization with coronary artery bypass grafting(CABG) has become established as the most effective interventional therapy for patients with moderately severe and severe stable ischemic heart disease(SIHD). this recommendation is based on traditional 5-year outcomes of mortality and avoidance of myocardial infarction leading to reintervention and/or cardiac death. However, these results are confounded in that they challenge the traditional CABG surgical tenets of completeness of anatomic revascularization, the impact of arterial revascularization on late survival, and the lesser impact of secondary prevention following CABG on late outcomes. Moreover, the emergence of physiologic-based revascularization with percutaneous cardiovascular intervention as an alternative strategy for revascularization in SIHD raises the question of whether there are similar physiologic effects in CABG. Finally, the ongoing ISCHEMIA trial is specifically addressing the importance of the physiology of moderate or severe ischemia in optimizing therapeutic interventions in SIHD. So it is time to address the role that physiology plays in surgical revascularization. the long-standing anatomic framework for surgical revascularization is no longer sufficient to explain the mechanisms for short-term and long-term outcomes in CABG. Novel intraoperative imaging technologies have generated important new data on the physiologic blood flow and myocardial perfusion responses to revascularization on an individual graft and global basis. Long-standing assumptions about technical issues such as competitive flow are brought into question by real-time visualization of the physiology of revascularization. Our underestimation of the impact of Guideline Directed Medical therapy, or Optimal Medical therapy, on the physiology of preoperative SIHD, and the full impact of secondary prevention on post-intervention SIHD, must be better understood. In this review, these issues are addressed through the

关键词： Coronary artery bypass grafting Arterial revascularization Myocardial perfusion Surgical outcomes Intraoperative imaging

Evaluation of utility in shoulder pathology:Correlating the American Shoulder and Elbow Surgeons and Constant scores to the EuroQoL

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World Journal of Orthopedics 2012年第3期3卷 20-24页

作者： Blaine t Bafus Richard E Hughes bruce S Miller James E Carpenter Department of Orthopaedic Surgery Cleveland Clinic Foundation Cleveland OH 44115-2325 United States Department of Orthopaedic Surgery University of Michigan Ann Arbor MI 48109-2200 United States

AIM: to study whether health utility scores can be derived from shoulder-specific ***: Authors investigated two questions:(1) do the American Shoulder and Elbow Surgeons(ASES) score and the Constant score correlate with the EuroQo L(EQ-5D), a measure of health utility?(2) can the ASES and Constant scores be obtained from a complete study sample without bias? thirty subjects with various shoulder diagnoses completed ASES, Constant, and EQ-5D instruments. Pearson correlations were calculated to assess the associations between EQ-5D score and ASES and Constant ***: the correlation between EQ-5D score and ASES score was 0.60(P t was 0.54 for EQ-5D and Constant scores(P tiple regression model containing ASES score, Constant score, age, and gender failed to adequately predict EQ-5D. Moreover, 25% of patients meeting the inclusion criteria did not complete the ASES questionnaire because they did not feel that specific questions, such as "do usual sport-list" and "throw ball overhand," applied to ***: Authors' results do not support the use of the ASES and Constant scores in predicting EuroQ ol health utility values. However, the Constant score was more suitable for this patient population because all patients were able to complete it.

关键词： Utility EuroQoL American Shoulder and Elbow Surgeons score Constant score Shoulder Outcomes