检索结果-南通市图书馆

c-myb is involved in CML progression and is a therapeutic target in the zebrafish CML model

Animal Models and Experimental Medicine 2024年第2期7卷 136-144页

作者： Yin Ye Xiaojun Yang Feifei Li Wei Liu Wenqing Zhang Zhibin Huang division of cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhouChina

Background:Despite the success of tyrosine kinase inhibitors in chronic myeloid leukemia(CML)therapy,CML still faces the challenges of drug resistance and progression to blast crisis.Twenty-five percent of patients have imatinib resistance and treatment difficulties due to heterogeneity after progression,but little is known about the mechanism.A key transcription factor in hematopoiesis,MYB,has been reported to increase abnormally in several types of aggressive blood disorders including CML.Methods:This study used a zebrafish model to explore the relationship between BCR/ABL1 and c-myb in CML progression.A CML zebrafish model was crossed with a c-myb hyperactivity transgenic line.Results:It was found that both exogenous BCR/ABL1 and c-myb could up-regulate the expression of neutrophil-related genes.More seriously,neutrophil accumulation was observed when BCR/ABL1 was combined with c-myb overexpression.Further studies showed that c-myb may be one of the downstream targets of BCR/ABL1 and the effect of BCR/ABL1 on neutrophils was c-myb dependent.Taking advantage of this inheritable in vivo model,it was shown that a combination of imatinib and flavopiridol,a cyclin-dependent kinase inhibitor targeting MYB,could more effectively alleviate the aggressive phenotype of the double transgene line.Conclusion:In summary,this study suggests that c-myb acts downstream of BCR/ABL1 and is involved in CML progression and is therefore a risk factor and a valuable target for the treatment of CML progression.The model used in the study could be helpful in high-throughput drug screening in CML transformation.

关键词： chronic myeloid leukemia c-myb flavopiridol zebrafish model

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Emerging role of cellular senescence in normal lung development and perinatal lung injury

引用

Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 10-16页

作者： Phyllis A.Dennery Hongwei Yao Department of Molecular biology Cell Biology&BiochemistryDivision of Biology and MedicineBrown UniversityProvidenceRI 02912USA Department of Pediatrics Warren Alpert Medical School of Brown UniversityProvidenceRI 02903USA

cellular senescence is a status of irreversible growth arrest,which can be triggered by the p53/p21cip1 and p16INK4/Rb pathways via intrinsic and external factors.Senescent cells are typically enlarged and flattened,and characterized by numerous molecular features.The latter consists of increased surfaceome,increased resid-ual lysosomal activity at pH 6.0(manifested by increased activity of senescence-associated beta-galactosidase[SA-𝛽-gal]),senescence-associated mitochondrial dysfunction,cytoplasmic chromatin fragment,nuclear lamin b1 exclusion,telomere-associated foci,and the senescence-associated secretory phenotype.These features vary depending on the stressor leading to senescence and the type of senescence.cellular senescence plays pivotal roles in organismal aging and in the pathogenesis of aging-related diseases.Interestingly,senescence can also both promote and inhibit wound healing processes.We recently report that senescence as a programmed pro-cess contributes to normal lung development.Lung senescence is also observed in Down Syndrome,as well as in premature infants with bronchopulmonary dysplasia and in a hyperoxia-induced rodent model of this disease.Furthermore,this senescence results in neonatal lung injury.In this review,we briefly discuss the molecular features of senescence.We then focus on the emerging role of senescence in normal lung development and in the pathogenesis of bronchopulmonary dysplasia as well as putative signaling pathways driving senescence.Finally,we discuss potential therapeutic approaches targeting senescent cells to prevent perinatal lung diseases.

关键词： Senescence Normal lung development Bronchopulmonary dysplasia Down syndrome Senolytics

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cancer-associated fibroblasts express CD1d and activate invariant natural killer T cells under cellular stress

引用

cellular & Molecular Immunology 2024年第1期21卷 91-94页

作者： Shengduo Pei Jonas Sjölund Yueyun Pan Kristian Pietras Mikael C.I.Karlsson Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholmSweden division of Translational Cancer Research Department of Laboratory MedicineLund University Cancer CentreLund UniversityLundSweden

Invariant natural killer T(iNKT)cells are part of the family of unconventional T cells,and they recognize glycolipid antigens presented on the MHC class I like molecule CD1^([1]).In humans there are five CD1 molecules named CD1a to CD1e,whereas mice use only CD1d for lipid presentation.Functionally,iNKT cells can elicit both cytotoxicity similarly to conventional CD8 T cells and secrete cytokines that influence the adaptive immune response including providing direct T cell help to B cells^([2]).In the context of tumors,they can use both release of granzyme B and use Fas-mediated mechanisms for killing of tumor cells.As iNKT cells use a restricted TCR repertoire and CD1 molecules are non-heterogenous the risk of graft vs host disease is limited and thus these T cells have been an attractive option for off the shelf immunotherapy to treat cancer^([3]).

关键词： killer CD1d Cancer

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Pandemic punch:SARS-CoV-2 hits pancreas

引用

Signal Transduction and Targeted Therapy 2024年第5期9卷 1779-1780页

作者： Ninel Azoitei Sandra Heller Alexander Kleger Institute of Molecular Oncology and Stem cell biology Ulm UniversityUlmGermany division of Interdisciplinary Pancreatology Clinic of Internal Medicine IUniversity Hospital UlmUlmGermany

The COVID-19 pandemic has profoundly impacted global health systems,revealing the extensive repercussions of SARS-CoV-2 beyond respiratory symptoms.Indeed,traditionally considered a respiratory virus,SARS-CoV-2’s showcased the ability to target multiple organ systems including pancreas,an organ crucial for regulating blood sugar levels and aiding digestion.

关键词： pancreas respiratory traditionally

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Identification and characterization of human hematopoietic mesoderm

引用

Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China CAMS Center for Stem cell Medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China division of cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage biases.It is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental stage.In this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic lineages.We discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM cells.Mechanistically,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its enhancer.Inhibition of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell differentiation.In conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Genetically modified pigs:Emerging animal models for hereditary hearing loss

引用

Zoological Research 2024年第2期45卷 284-291页

作者： Xiao Wang Tian-Xia Liu Ying Zhang Liang-Wei Xu Shuo-Long Yuan A-Long Cui Wei-Wei Guo Yan-Fang Wang Shi-Ming Yang Jian-Guo Zhao State Key Laboratory of Stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China Institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem cell and Regenerative Medicine Beijing 100101China Department of Otolaryngology-Head and Neck Surgery Institute of OtolaryngologyChinese PLA General HospitalBeijing 100853China division of Life Sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230022China State Key Laboratory of Animal Biotech Breeding Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing100193China

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

关键词： Pigs Animal models Hereditary hearing loss Genetic modification Inner ear

来源：

维普期刊数据库

同方期刊数据库博看期刊评论

在线全文

学校读者我要写书评

暂无评论

Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

引用

Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： Antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

引用

中华医学杂志(英文版) 2024年第10期137卷 1207-1217页

作者： Pan Tianzhong Ding Peng Huang Aijie Tang Baolin Song Kaidi Sun Guangyu Wu Yue Yang Shiying Chen Xingchi Wang Dongyao Zhu Xiaoyu Department of Hematology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China Anhui Provincial Key Laboratory of Blood Research and Applications Hefei Anhui China Blood and cell Therapy Institute Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China

Background: With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods: A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results: The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year (F = 4.684,P = 0.039 andF = 5.583,P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93;P = 0.031).Conclusions: Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

关键词： Umbilical cord blood transplantation Graft-versus-host disease Immune reconstitution Double negative T Hematological Malignancies Treg cell Breg cell

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies

引用

Cancer biology & Medicine 2024年第4期21卷 331-346页

作者： Shuangcheng Li Tianci Wang Xinghui Xiao Xiaodong Zheng Haoyu Sun Rui Sun Hongdi Ma Zhigang Tian Xiaohu Zheng Hefei National Research Center for Physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Immunology University of Science and Technology of ChinaHefei 230027China Hefei TG ImmunoPharma Corporation Limited Hefei 230601China Research Unit of NK cell Study Chinese Academy of Medical SciencesBeijing 100864China Key Laboratory of Quantitative Synthetic biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

关键词： NK cell CD300A phosphatidylserine immune checkpoint hematologic malignancy

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Unveiling the distinctive traits of functional rye centromeres:minisatellites, retrotransposons, and R-loop formation

引用

Science China Life Sciences 2024年

作者： Chang Liu Shulan Fu Congyang Yi Yang Liu Yuhong Huang Xianrui Guo Kaibiao Zhang Qian Liu James A.Birchler Fangpu Han State Key Laboratory of Plant cell and Chromosome Engineering Institute of Genetics and Developmental Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Key Laboratory for Plant Genetics and Breeding Sichuan Agricultural University division of Biological Science University of MissouriColumbia

Centromeres play a vital role in cellular division by facilitating kinetochore assembly and spindle attachments. Despite their conserved functionality, centromeric DNA sequences exhibit rapid evolution, presenting diverse sizes and compositions across species. The functional significance of rye centromeric DNA sequences, particularly in centromere identity, remains unclear. In this study, we comprehensively characterized the sequence composition and organization of rye centromeres. Our findings revealed that these centromeres are primarily composed of long terminal repeat retrotransposons(LTR-RTs) and interspersed minisatellites. We systematically classified LTR-RTs into five categories, highlighting the prevalence of younger CRS1, CRS2, and CRS3 of CRSs(centromeric retrotransposons of Secale cereale) were primarily located in the core centromeres and exhibited a higher association with CENH3 nucleosomes. The minisatellites, mainly derived from retrotransposons, along with CRSs, played a pivotal role in establishing functional centromeres in rye. Additionally, we observed the formation of R-loops at specific regions of CRS1, CRS2, and CRS3, with both rye pericentromeres and centromeres exhibiting enrichment in R-loops. Notably, these R-loops selectively formed at binding regions of the CENH3 nucleosome in rye centromeres, suggesting a potential role in mediating the precise loading of CENH3 to centromeres and contributing to centromere specification. Our work provides insights into the DNA sequence composition, distribution, and potential function of R-loops in rye centromeres. This knowledge contributes valuable information to understanding the genetics and epigenetics of rye centromeres, offering implications for the development of synthetic centromeres in future plant modifications and beyond.

关键词：

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：