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Combined Antitumor Effect of Ursolic Acid And 5-Fluorouracil on Human Esophageal Carcinoma cell Eca-109 In Vitro

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Chinese Journal of Cancer Research 2010年第1期22卷 62-67页

作者： Guo-qing Chen Zhen-wei Yao Wei-ping Zheng Li Chen Hong Duan Yi Shen Research center of Tissue Engineering and stem cell Department of Pathophysiology Chongqing Medical University Chongqing 400016 China department of Obsttrics and Gynecology the First Affiliated Hospital Chongqing Medical University Chongqing 400016 China

Objective： To study the combined antitumor effect and possible mechanisms of ursolic acid with 5-fluorouracil （5-FU） on human esophageal carcinoma cell Eca-109 in vitro. Methods： Eca-109 cells were treated with ursolic acid （10-50 μmol/L） and/or 5-fluorouracil （48.0-768.8 μmol/L） for 48 h in vitro. And then cell proliferation was determined by MTT assay. cell cycle and apoptosis rate were analyzed by flow cytometry （FCM）. The morphological changes of apoptosis were observed by fluorescent microscopy. At last the expression of P27kipl, bcl-2 and bax were detected by western blot. Results： Results： In comparison with single agent treatment, the combination of ursolic acid and 5-fluorouracil produced greater efficacy in growth inhibition, cell cycle arrest at G0/G1 phase, and apoptosis induction （P〈0.05）. Western blot analysis showed that the combination use of ursolic acid and 5-fluorouracil suppressed the expression of bcl-2 and increased the expressions of bax and P27kip1. Conclusion： Ursolic acid combined with 5-fluorouracil showed adjuvant antiproliferative effects on human esophageal carcinoma cell Eca-109 in vitro, which mainly due to the induction of cell cycle arrest as well as apoptosis.

关键词： Ursolic acid 5-fluorouracil Eca-109 cells Apoptosis cell cycle P27kip1

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Tubulin detyrosination promotes human trophoblast syncytium formation

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Journal of Molecular cell biology 2019年第11期11卷 967-978页

作者： Rui Wang Ruoxuan Yu Cheng Zhu Hai-Yan Lin Xiaoyin Lu Hongmei Wang State Key Laboratory of stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijingChina department of Experimental Radiation Oncology the University of Texas MD Anderson Cancer CenterHoustonTXUSA University of Chinese Academy of Sciences BeijingChina

Human trophoblast syncytialization is one of the most important yet least understood events during placental *** this study,we found that detyrosinated a-tubulin(detyr-a-tub),which is negatively regulated by tubulin tyrosine Ugase(TTL),was elevated during human placental cytotrophoblast ***,relatively high expression of TTL protein was observed in first-trimester human placental cytotrophoblast cells,but fusing trophoblast cells exhibited much lower levels of T T L Notably,fusion of preeclamptic cytotrophoblast cells was compromised but could be partially rescued by knockdown of TTL ***,chronic downregulation of TTL in trophoblast cells resulted in significantly elevated expression of *** of detyr-a-tub thus contributed to the cell surface localization of the fusogenic protein Syncytin-2 and the gap junction protein Connexin 43(Cx43),which in turn promoted successful fusion between trophoblast *** together,the results suggest that tubulin detyrosination plays an essential role in human trophoblast fusogenic protein aggregation and *** tubulin detyrosination leads to defects in syncytialization and potentially to the onset of preeclampsia.

关键词： TTL detyrosination syncytialization preeclampsia placenta syncytin

A targetable pathway to eliminate TRA-1-60^(+)/TRA-1-81^(+)chemoresistant cancer cells

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Journal of Molecular cell biology 2023年第6期15卷 25-39页

作者： Lei Tan Xiaohua Duan Pratyusha Mutyala Ting Zhou Sadaf Amin Tuo Zhang Brian Herbst Gokce Askan Tomer Itkin Zhaoying Xiang Fabrizio Michelassi Michael D.Lieberman Christine AIacobuzio-Donahue Steven DLeach Todd Evans Shuibing Chen department of Surgery Weill Cornell MedicineNew YorkNY 10065USA center for Energy Metabolism and Reproduction Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China center for Genomic Health Weill Cornell MedicineNew YorkNY 10065USA The SKI stem cell Research Facility The Center for Stem Cell Biology and Developmental Biology ProgramMemorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Genomic Resource Core Facility Weill Cornell Medical CollegeNew YorkNY 10065USA Rubenstein center for Pancreatic Cancer Research Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Division of Regenerative Medicine Hartman Institute for Therapeutic Organ RegenerationAnsary Stem Cell InstituteDepartment of MedicineWeill Cornell MedicineNew YorkNY 10065USA Dartmouth Cancer center Darmouth CollegeHanoverNH 03755USA

Chemoresistance is a primary cause of treatment failure in pancreatic *** cell surface markers specifically expressed in chemoresistant cancer cells(CCCs)could facilitate targeted therapies to overcome *** performed an antibody-based screen and found that TRA-1-60 and TRA-1-81,two‘stemness’cell surface markers,are highly enriched in ***-more,TRA-1-60^(+)/TRA-1-81^(+)cells are chemoresistant compared to TRA-1-60^(-)/TRA-1-81^(-)*** profiling identified UGT1A10,shown to be both necessary and sufficient to maintain TRA-1-60/TRA-1-81 expression and *** a high-content chemical screen,we identified Cymarin,which downregulates UGT1A10,eliminates TRA-1-60/TRA-1-81 expression,and increases chemosensitivity both in vitro and in ***,TRA-1-60/TRA-1-81 expression is highly specific in primary cancer tissue and positively correlated with chemoresistance and short survival,which highlights their potentiality for targeted ***,we discovered a novel CCC surface marker regulated by a pathway that promotes chemoresistance,as well as a leading drug candidate to target this pathway.

关键词： pancreatic cancer TRA-1-60/TRA-1-81 chemoresistance UGT1A10 Cymarin

Fluorescent probes for the detection of reactive oxygen species in human spermatozoa

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Asian Journal of Andrology 2020年第5期22卷 465-471页

作者： Sara Escada-Rebelo Francisca G Mora Ana P Sousa Teresa Almeida-Santos Artur Paiva Joao Ramalho-Santos phD Programme in Experimental biology and Biomedicine CNC-Center for Neuroscience and Cell BiologyUniversity of CoimbraCoimbra 3004-504Portugal biology of Reproduction and stem cell Group CNC-Center for Neuroscience and Cell BiologyUniversity of CoimbraCoimbra 3004-504Portugal IIIUC-Institute for Interdisciplinary Research Casa Costa AlemaoUniversity of CoimbraCoimbra 3030-789Portugal Reproductive Medicine Unit University Hospitals of CoimbraCoimbra 3004-561Portugal Faculty of Medicine University of CoimbraCoimbra 3000-370Portugal Clinical Pathology Unit University Hospitals of CoimbraCoimbra 3004-561Portugal department of Life Sciences University of CoimbraCoimbra 3000-456Portugal

Reactive oxygen species(ROS)production is a by-product of mitochondrial activity and is necessary for the acquisition of the capacitated state,a requirement for functional ***,an increase in oxidative stress,due to an abnormal production of ROS,has been shown to be related to loss of sperm function,highlighting the importance of an accurate detection of sperm ROS,given the specific nature of this *** this work,we tested a variety of commercially available fluorescent probes to detect ROS and reactive nitrogen species(RNS)in human sperm,to define their *** both flow cytometry(FC)and fluorescence microscopy(FM),we confirmed that MitoSOX™Red and dihydroethidium(DHE)detect superoxide anion(as determined using antimycin A as a positive control),while DAF-2A detects reactive nitrogen species(namely,nitric oxide).For the first time,we also report that RedoxSensor™Red CC-1,cellROX®Orange Reagent,and MitoPYl seem to be mostly sensitive to hydrogen peroxide,but not ***,mean fluorescence intensity(and not percentage of labeled cells)is the main parameter that can be reproducibly monitored using this type of methodology.

关键词： flow cytometry fluorescent probes human spermatozoa oxidative stress reactive oxygen species

Single-cell transcriptomic landscape of human blood cells

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National Science Review 2021年第3期8卷 42-52页

作者： Xiaowei Xie Mengyao Liu Yawen Zhang Bingrui Wang Caiying Zhu Chenchen Wang Qing Li Yingying Huo Jiaojiao Guo Changlu Xu Linping Hu Aiming Pang Shihui Ma Lina Wang Wenbin Cao Shulian Chen Qiuling Li Sudong Zhang Xueying Zhao Wen Zhou Hongbo Luo Guoguang Zheng Erlie Jiang Sizhou Feng Lixiang Chen Lihong Shi Hui Cheng Sha Hao Ping Zhu Tao Cheng State Key Laboratory of Experimental Hematology and National Clinical Research center for Blood Diseases Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences &Peking Union Medical College center for stem cell Medicine and department of stem cell & Regenerative Medicine Chinese Academy of Medical Sciences and Peking Union Medical College Cancer Research Institute School of Basic Medical Science Central South University School of Life Sciences Zhengzhou University

High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying ***,an elaborate and comprehensive transcriptome reference of the whole blood system is ***,we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types,including hematopoietic stem cells,progenitors and mature blood cells derived from 21 healthy *** high sequencing depth and coverage,we constructed a single-cell transcriptional atlas of blood cells(ABC) on the basis of both protein-coding genes and long noncoding RNAs(lncRNAs),and showed a high consistence between ***,putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were *** common transcription factor regulatory networks were activated in neutrophils and monocytes,lymphoid cells dramatically changed their regulatory networks during ***,we showed a subset of nucleated erythrocytes actively expressing immune signals,suggesting the existence of erythroid precursors with immune ***,a web portal offering transcriptome browsing and blood cell type prediction has been ***,our work provides a transcriptional map of human blood cells at single-cell resolution,thereby offering a comprehensive reference for the exploration of physiological and pathological hematopoiesis.

关键词： human hematopoietic cells lncRNAs transcription factor single-cell RNA-seq

Out of step： The function of TALE homeodomain transcription factors that regulate shoot meristem maintenance and meristem identity

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Frontiers in biology 2012年第2期7卷 144-154页

作者： Shang WU Harley M. S. SMITH center for Plant cell biology Institute of Integrative Genome Biology Department of Botany and Plant Sciences University of CaliforniaRiverside CA 92521 USA

The indeterminate growth pattern displayed by shoots is mediated by the proper maintenance of the shoot meristem. Meristem maintenance is dependent upon the balance of stem cell perpetuation in the central zone （CZ） and organogenesis in the peripheral zone （PZ）. Although the mechanisms that coordinate CZ and PZ function is not understood, meristem cell fate is likely achieved by the spatial interplay between gene regulatory networks and hormone signaling pathways. During shoot maturation, the identity of the shoot meristem as well as the lateral organs are transformed during the vegetative and reproductive transitions. Studies in model plant systems indicate that three amino acid extension （TALE） homeodomain proteins integrate signaling events that transform the identity of the shoot meristem and establish reproductive patterns of growth. This review will highlight the function of TALE homeodomain transcription factors that regulate shoot meristem cell fate and also function with phase specific regulators to maintain shoot meristem identity.

关键词： shoot development meristem flowering patterning homeodomain

The Role of KDM2A and H3K36me2 Demethylation in Modulating MAPK Signaling During Neurodevelopment

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Neuroscience Bulletin 2024年第8期40卷 1076-1092页

作者： Zongyao Ren Haiyan Tang Wendiao Zhang Minghui Guo Jingjie Cui Hua Wang Bin Xie Jing Yu Yonghao Chen Ming Zhang Cong Han Tianyao Chu Qiuman Liang Shunan Zhao Yingjie Huang Xuelian He Kefu Liu Chunyu Liu Chao Chen center for Medical Genetics&Hunan Key Laboratory of Medical Genetics School of Life Sciencesand Department of PsychiatryThe Second Xiangya HospitalCentral South UniversityChangsha 410028China National Clinical Research center on Mental Disorders The Second Xiangya HospitalCentral South UniversityChangsha 410028China National Clinical Research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410011China Furong Laboratory Changsha 410000China department of Psychiatry SUNY Upstate Medical UniversitySyracuseNY 13210USA Precision Medical center Wuhan Children's Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430014China department of Medical Genetics Hunan Children's HospitalChangsha 410007China

Intellectual disability(ID)is a condition characterized by cognitive impairment and difficulties in adaptive *** our research,we identified two de novo mutations(c.955C>T and c.732C>A)at the KDM2A locus in individuals with varying degrees of *** addition,by using the Gene4Denovo database,we discovered five additional cases of de novo mutations in *** mutations we identified significantly decreased the expression of the KDM2A *** investigate the role of KDM2A in neural development,we used both 2D neural stem cell models and 3D cerebral *** findings demonstrated that the reduced expression of KDM2A impairs the proliferation of neural progenitor cells(NPCs),increases apoptosis,induces premature neuronal differentiation,and affects synapse *** ChIP-Seq analysis,we found that KDM2A exhibited binding to the transcription start site regions of genes involved in *** addition,the knockdown of KDM2A hindered H3K36me2 binding to the downstream regulatory elements of *** integrating ChIP-Seq and RNA-Seq data,we made a significant discovery of the core genes'remarkable enrichment in the MAPK signaling ***,this enrichment was specifically linked to the p38 MAPK ***,disease enrichment analysis linked the differentially-expressed genes identified from RNA-Seq of NPCs and cerebral organoids to neurodevelopmental disorders such as ID,autism spectrum disorder,and ***,our findings suggest that KDM2A plays a crucial role in regulating the H3K36me2 modification of downstream genes,thereby modulating the MAPK signaling pathway and potentially impacting early brain development.

关键词： Intellectual disability KDM2A Neurodevelopmental disorder Cerebral organoids

Complete blood and urine paraprotein tests as response assessments in multiple myeloma patients treated with bortezomib,cyclophosphamide,and dexamethasone

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Chronic Diseases and Translational Medicine 2024年第1期10卷 62-68页

作者： Xialu Lan Fujing Zhang Chen Yang Wei Su Jianhua Du Shuangjiao Liu Miao Chen Bing Han Daobin Zhou Junling Zhuang department of Hematology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina department of Pathology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouChina department of Laboratory Medicine Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina

Background: This study assessed the effect of standardized efficacy markers on prognosis in patients with newly diagnosed multiple myeloma(MM)during the induction phase of treatment with bortezomib,cyclophosphamide,and dexamethasone(BCD).Methods :We retrospectively analyzed clinical data in 197 newly diagnosed MM patients treated with BCD as front-line regimen at Peking Union Medical College Hospital from January 1,2013 to December 31,***: There were 107 patients with International Staging System(ISS)III and 51 with paraprotein of light *** these,77 completed nine cycles of the BCD *** the number of treatment cycles increased,the proportions of serum and urine immunofixation electrophoresis(IFE)tests elevated from 40.39%to 62.22%and 16.75%to 37.78%,*** than 90%of intact immunoglobulin chain MM patients were evaluated for blood M protein per cycle,but that of urinary M protein was less than 60%.The detection rate of urinary M protein in light chain MM was more than 70%per *** with a very good partial response(VGPR)had longer progression-free survival(PFS)than those with uncertain VGPR(32 vs.26 months,p=0.0336).Of the 141 patients who completed at least four cycles without undergoing autologous hematopoietic stem cell transplantation,those who were regularly assessed at every other cycle showed more favorable PFS than those who visited irregularly(27 vs.22 months,p=0.059).Conclusion: Urinary M protein detection rate is significantly lower than that in serum,leading to an overestimation of efficacy,premature reduction of treatment intensity,and shortened *** response assessments are critical to treatment decisions and clinical diagnoses.

关键词： bortezomib light chain subtype multiple myeloma response assessment

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Reprogrammed astrocytes with old‘memories’blossom into region-specific neurons

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Protein & cell 2011年第2期2卷 87-89页

作者： Anuja Ghorpade department of cell biology and Anatomy University of North Texas Health Science Center3500 Camp Bowie BlvdFort WorthTX 76107USA

Almost a decade after Dolly the sheep changed the history of biological clock turning,Takahashi and Yamanaka made headlines both in scientific journals,and in magazines such as TIME,by once again proving that the clock could be turned back,even on somatic cells,by‘direct reprogramming.’(Takahashi and Yamanaka,2006;Park,2007;Takahashi et al.,2007)During the last decade,stem cells have been at the forefront of science,politics and the public forums due to the conflicting issues surrounding the use of embryonic stem cells in research and regenerative medicine strategies.

关键词： turning programming. specific

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