检索结果-南通市图书馆

Activation ofγ-globin expression by a common variant disrupting IKAROS-binding motif inβ-thalassemia

Journal of Genetics and Genomics 2025年第2期52卷 157-167页

作者： Hualei Luo Jueheng Wang Lang Qin Xinhua Zhang Hailiang Liu Chao Niu Mengyang Song Congwen Shao Peng Xu Miao Yu Haokun Zhang Yuhua Ye Xiangmin Xu Innovation Center for Diagnostics and Treatment of thalassemia Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of Medical Genetics School of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China State Key Laboratory of Genetic Engineering School of Life SciencesFudan UniversityShanghai 201114China Department of Pediatrics 923rd Hospital of the People's Liberation ArmyNanningGuangxi 530021China Cyrus Tang Medical Institute National Clinical Research Centre for Hematologic DiseasesCollaborative Innovation Centre of HematologyState Key Laboratory of Radiation Medicine and ProtectionSoochow University SuzhouSuzhouJiangsu 215031China State Key Laboratory of Genetic Engineering MOE Engineering Research Center of Gene TechnologySchool of Life SciencesFudan UniversityShanghai 200438China

Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this *** of cis-or trans-acting mutations contributing to the diverse extent of fetal hemoglobin(Hb F)might illustrate the underlying mechanism ofγ-β-globin ***,we recruit a cohort of 1142β-thalassemia patients and dissect the natural variants in the wholeβ-globin gene cluster through a targeted next-generation sequencing panel.A previously unreported SNP rs7948668,predicted to disrupt the binding motif of IKAROS as a key component of chromatin remodeling complexes,is identified to be significantly associated with higher levels of Hb F and age at ***-editing on this SNP leads to the elevation of Hb F in both HUDEP-2 and primary CD34+cells while the extent of elevation is amplified in the context ofβ-thalassemia mutations,indicating epistasis effects of the SNP in the regulation of Hb ***,we perform ChIP-qPCR and 4C assays to prove that this variant disrupts the binding motif of IKAROS,leading to enhanced competitiveness of HBG promoters to locus control *** study highlights the significance of common regulatory SNPs and provides potential targets for treatingβ-hemoglobinopathy.

关键词： β-thalassemia Fetal hemoglobin Single nucleotidepolymorphism IKAROS Locus control region

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

Changes in IncRNAs and related genes in β-thalassemia minor and β-thalassemia major

引用

Frontiers of Medicine 2017年第1期11卷 74-86页

作者： Jing Ma Fei Liu Xin Du Duan Ma Likuan Xiong Central Laboratory Bao 'an Maternal and Children Health Hospital Key Laboratory of Birth Defects Research Birth Defects Prevention Research and Transformation Team Shenzhen 518000 China Key Laboratory of Metabolism and Molecular Medicine Ministry of Education Department of Biochemistry and Molecular Biology Institute of Medical Sciences School of Basic Medical Sciences Fudan University Shanghai 200032 China Department of Hematology The Second People's Hospital Shenzhen 518035 China

β-thalassemia is caused by β-globin gene mutations. However, heterogeneous phenotypes were found in individuals with same genotype, and still undescribed mechanism underlies such variation. We collected blood samples from 30 β-thalassemia major, 30 β-thalassemia minor patients, and 30 matched normal controls. Human lncRNA Array v2.0 （8 × 60 K, Arraystar） was used to detect changes in long non-coding RNAs （lncRNAs） and mRNAs in three samples each from β-thalassemia major, β-thalassemia minor, and control groups. Compared with normal controls, 1424 and 2045 lncRNAs were up- and downregulated, respectively, in β-thalassemia major patients, whereas 623 and 349 lncRNAs were up- and downregulated, respectively, in β-thalassemia minor patients. Compared with β-thalassemia minor group, 1367 and 2356 lncRNAs were up- and downregulated, respectively, in β-thalassemia major group. We selected five lncRNAs that displayed altered expressions （DQ583499, X-inactive specific transcript （Xist）, IincRNA-TPM1, MRFS16P, and lincRNA-RUNX2-2） and confirmed their expression levels in all samples using real-time polymerase chain reaction. Based on coding-non-coding gene co-expression network and gene ontology biological process analyses, several signaling pathways were associated with three common organ systems exhibiting β-thalassemia phenotypes： hematologic, skeletal, and hepatic systems. This study implicates that abnormal expression levels of lncRNAs and mRNA in β-thalassemia cases may be correlated with its various clinical phenotypes.

关键词： β-thalassemia long non-coding RNA mRNA phenotypic heterogeneity pathway

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

Correction of β-thalassemia mutant by base editor in human embryos

引用

Protein & Cell 2017年第11期8卷 811-822页

作者： Puping Liang Chenhui Ding Hongwei Sun Xiaowei Xie Yanwen Xu Xiya Zhang Ying Sun Yuanyan Xiong Wenbin Ma Yongxiang Liu Yali Wang Jianpei Fang Dan Liu Zhou Songyang Canquan Zhou Junjiu Huang Key Laboratory of Gene Engineering of the Ministry of Education Guangzhou Key Laboratory of Healthy Aging Research and State Key Laboratory of Biocontrol SYSU-BCM Joint Research Center School of Life Sciences Sun Yat-sen University Guangzhou 510275 China Key Laboratory of Reproductive Medicine of Guangdong Province School of Life Sciences and the First Affiliated Hospital Sun Yat-sen University Guangzhou 510275 China Department of Pediatrics Second Affiliated Hospital Sun Yat-sen University Guangzhou 510120 China Verna and Marrs Mclean Department of Biochemistry and Molecular Biology Baylor College of Medicine One Baylor Plaza Houston. TX 77030. USA

β-thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 （A〉G） mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor （BE） system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 （A〉G） mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 （A〉G） homozygous mutation. Data showed that base editor could precisely correct HBB -28 （A〉G） mutation in the patient＇s primary cells. To model homozygous mutation disease embryos, we consb＇ucted nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured （IVM） ***, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.

关键词： β-thalassemia HBB -28 (A〉G) baseeditor human embryo

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

Treatment of β-thalassemia With Hydroxyurea (HU)——Effects of HU on Globin Gene Expression

引用

Science China Chemistry 1994年第11期37卷 1350-1359页

作者：黄淑帧任兆瑞陈美珏许洪平曾溢滔 G.P.Rodgers 曾凡一 A.N.Schechter Shanghai Institute of Medical Genetics Shanghai Children's HospitalShanghai 200040PRC Laboratory ofChemical Biology National Institute of DiabetesDigestive and Kidney DiseasesNIHMD 20892USA

A newly developed method of RT-PCR/competitive PCR for measuring the relative and ab-solute content of globin mRNAs as well as micro-globin chain biosynthetic assay have been used to study thealterations of globin gene expressions in the patients with β-thalassemia pre-and post-hydroxyurea(HU)*** was found for the first time that HU had the effect of enhancing β-globin gene expression insome *** cases with β-thalassemia who were subjected to HU treatment for over two years showeda marked increase in β-globin mRNA level and β-globin chain synthesis,resulting in more effective erythro-poiesis and the alleviation of clinical symptoms.

关键词： β-thalassemia globin gene expression hydroxyurea

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

Hematopoietic stem cell transplantation for children with β-thalassemia major: multicenter experience in China

引用

World Journal of Pediatrics 2018年第1期14卷 92-99页

作者： Xin-Yu Li Xin Sun Jing Chen Mao-Quan Qin Zuo Luan Yi-Ping Zhu Jian-Pei Fang Guangdong Provincial Key Laboratory of MalignantTumor Epigenetics and Gene Regulation Medical ResearchCenter(Pediatrics)Medical Research CenterSun Yat-SenMemorial HospitalSun Yat-Sen UniversityGuangzhouChina Department of Hematology Guangzhou Womenand Children’s Medical CenterGuangzhou MedicalUniversityGuangzhouChina Department of Hematology Shanghai Children’s MedicalCenterShanghai Jiaotong University School of MedicineShanghaiChina

Backgroundβ-thalassemia major (β-TM) has become a public health problem in China's Mainland. Hematopoietic stem cell transplantation (HSCT) has remained the only cure forβ-TM in China's Mainland since 1998. Methods This multicenter retrospective study provides a comprehensive review of the outcomes of 50 pediatric patients withβ-TM who received HSCT between 1998 and 2009 at five centers in China's Mainland. Both related (n = 35) and unrelated donors (n = 15) with complete human leukocyte antigen matches were included. The stem cell sources included bone mar-row (BM), peripheral blood stem cells, umbilical cord blood (UCB) and a combination of BM and UCB or a combination of BM and peripheral blood stem cells from a single sibling donor. Results The probabilities of 5-year overall survival (OS) and thalassemia-free survival (TFS) after the first HSCT were 83.1 and 67.3%, respectively. Graft failure (GF) occurred in 17 patients. Univariate analyses showed that umbilical cord blood transplantation (UCBT) was one of the potential risk factors for decreased OS (P = 0.051), and that UCBT (P = 0.002) was potentially related to TFS. GF incidence was distinct between the UCBT and non-UCBT groups (P = 0.004). Four cases of UCB-BM combined transplantation led to decreased risks of mortality and recurrence. In the UCBT group, related donor transplantation produced more favorable results than unrelated donor transplantation in OS (P = 0.009) but not in TFS (P = 0.217). Conclusions GF was the primary cause of UCBT failure. Though UCBT from related donors was not favorable, the combined transplantation of UCB and BM could improve the prognosis of UCBT.

关键词： β-thalassemia major Hematopoietic stem cell transplantation Umbilical cord blood

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

Myeloproliferative neoplasms complicated withβ-thalassemia:Two case report

引用

World Journal of Clinical Cases 2022年第29期10卷 10655-10662页

作者： Neng-Wen Xu Lin-Jie Li Department of Hematology College of MedicineLishui HospitalZhejiang UniversityLishui 323000Zhejiang ProvinceChina

BACKGROUND BCR-ABL-negative myeloproliferative neoplasms(MPNs)are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more myeloid lineages and by mutually exclusive JAK2 V617F,CALR,and MPL[A1]*** combination of MPN and thalassemia is extremely *** cases with myeloproliferative neoplasms andβ-thalassemia have been ***,these have not been extensively *** present report describes two cases of myeloproliferative neoplasms complicated withβ-thalassemia and reviews all similar cases reported in the *** SUMMARY We report two patients who were diagnosed with myeloproliferative neoplasms complicated withβ-*** patients had abnormal increases in platelet *** on bone marrow pathology and molecular biology assessment,we made the diagnosis of myeloproliferative neoplasms complicated withβ-*** female patient was given hydroxyurea and interferon,which enabled good control of her blood counts;the male patient was given ruxolitinib tablets,thalidomide tablets,and interferon to control the condition,but the patient poorly responded to drug treatment and died of gastrointestinal bleeding six months *** Given the findings of our cases and the literature review,we hypothesize that myeloproliferative neoplasms complicated withβ-thalassemia can lead to rapid disease progression and a poor prognosis.

关键词： Myeloproliferative Neoplasms β-thalassemia Somatic gene mutation Germline gene mutation Case report

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

Genomewide DNA Methylation Responses in Patients with β-thalassemia Treated with Yisui Shengxue Granules (益髓生血颗粒)

引用

Chinese Journal of Integrative Medicine 2019年第7期25卷 490-496页

作者： CHENG Yan-ling ZHANG Xin-hua SUN Yu-wen WANG Wen-juan HUANG Jie CHU Na-li FANG Su-ping WU Zhi-kui Molecular Biology Labaratory South of Guang'anmen Hospital China Academy of Chinese Medical Sciences Beijing (102618) China Department of Hematology 303rd Hospital of People's Liberatory Army Nanning (530021) China Molecular Biology Laboratory of Guang'anmen Hospital China Academy of Chinese Medical Sciences Beijing (100053) China School of Traditional Chinese Medicine Capital Medical University Beijing (100069) China

Objective: To examine the clinical effects of Yisui Shengxue Granules(益髓生血颗粒) in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels. Methods: A randomized placebo-controlled double-blinded trial was conducted. Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group(12 g/bag, 3 times a day) during a 3-month intervention. Before and after 1, 2, and 3 months of treatment, peripheral intravenous blood was sampled, and blood parameters such as hemoglobin(Hb), red blood cells(RBCs), reticulocytes(Ret), and fetal hemoglobin(HbF) were analyzed. Mononuclear cells from 5 patients, who showed an obvious treatment effect, were isolated by density gradient centrifugation. DNA methylation was analyzed using an Affymetrix USA GeneChip Human Promoter 1.0 Array and Input-promoter 1.0. Results: Compared with pre-treatment, there was an obvious increase in Hb and RBCs counts after 1, 2, and 3 months in the experiment group(P<0.01 or P<0.05). Meanwhile, HbF increased from the 2 nd to the 3 rd month(P<0.05). In the control group, Hb and RBCs showed no obvioas change. After 3-month treatment, DNA methylation results from 5 patients revealed that there were 24 hypomethylated genes and 3,685 hypermethylated genes compared with pre-treatment. Genes of insulin-like growth factor 1 receptor(IGF1 R) and Janus kinase 3(JAK3) revealed the most relations with other genes(degree: 21) and genes of 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma 2(PLCG2) and mitogen-activated protein kinase 10(MAPK10) showed a stronger intermediary role(betweenness centrality=0.04). Conclusions: JAK3 and MAPK10 are two key genes in bone marrow and the lymphatic system, and JAK3 is likely to be related to hematopoietic cytokines in the process of early h

关键词： β-thalassemia Yisui Shengxue Granule Chinese medicine DNA-methylation

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

β-thalassemia mutations among children with anemia in Nanning city,China

β-Thalassemia mutations among children with anemia in Nanni...

引用

第十二次全国医学遗传学学术会议

作者： Sheng He Xuan Shang Dongming Li Qiang Zhang Yanqing Tang Yunli Lai Qiuli Chen Chenguang Zheng Prenatal Diagnostic Center GuangxiGuangxi Zhuang Automonous Region Women and Children Care Hospital Department of Medical Genetics School of Basical SciencesSouthern Medical University

Introduction:β-thalassemia is a common genetic disorder in Southern of China. The aim of this retrospective study is to analyze the frequency ofβ-thalassemia among Children in Nanning City,which is one of the biggest cities located in southern of *** and methods:Data from 2685 children with symptoms of anemia were *** blood samples were collected into EDTA-containing tubes and hematological parameters were analyzed using an automatic cell *** performance liquid chromatography technique was used to determine the type of *** screening of theβ-globin gene was performed withβ-Globin Strip ***:Of 2685 cases,929 were diagnosed asβ-*** rates of occurrence reached to 34.60%.A total of 13 kinds of genotype were *** genotypes of CD41-42(-TCTT)/N and CD17(A→T))/N CD41-42(-TCTT)/N and CD17(A→T))/N were most common,with the frequencies of 37.46%) and 25.19%respectively. 10 differentβ-thalassemia mutations were *** mutations in order of frequency were CD41-42(-CTTT)(46.59%),CD17(A→T)(28.03%),IVS-Ⅱ-654(C→T)(8.28%),CD71-72(+A) (6.10%),-28(A→G)(4.82%),CD26(G→A)(3.37%),and IVS-I-1(G→T)(2.27%).Anther three mutations were less frequent or sporadic including CD43(G→T)(0.36%),CD27-28(+C) and -29(A→G).Conclusions:The incidence of mutations of P-thalassemia among children was *** still seem to be a public health issue in Guangxi,China,indicating the government should pay more attention to this disease,and the necessity of a screening thalassemia program is urgent and more important.

关键词： β-thalassemia mutations Children anemia

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Clinical Efficacy and Molecular Mechanism of Nourishing Shen and Supplementing Marrow Principle in Treating β thalassemia

引用

Chinese Journal of Integrated Traditional and Western Medicine 2003年第4期9卷 248-253页

作者：吴志奎方素萍张新华蔡辉国王蕾易杰柴立民吕鑫霞陈玉英黄有文王荣新陈佩珍 DepartmentofMolecular-Biology Guang‘anmenHospi-talChinaAcademyofTraditionalChineseMedicineBei-Jing100053 不详 The303HospitolofPLA InstituteofHematology ChineseAcademyofMedicalSciencesCorrespondence

Objective: To explore the possibility of using traditional Chinese medicine (TCM) in treating β thalassemia, its clinical effect and molecular mechanism of the ***: According to the TCM theory of“Shen producing marrow”, the composite recipe, Yisui Shenxueling Granule (YSSXL), consisting of Chinese drugs for nourishing Shen and supplementing marrow (NS&SM) was given orally to 7 8 patients with β thalassemia (49 of the severe type and 29 of moderate type ), 3 times a day, 10 g each time (for children, the dose would be reduced proper ly), with 3 months as one therapeutic course, and no blood transfusion used in t he course. The clinical therapeutic efficacy and hematologic parameters in patie nts were observed, and systemic gene analysis was conducted with PAGE, PCR, PCR SSCP, RT PCR and DNA sequences analysis and mRNA detection, in order to s tudy the molecular mechanism from the relationships between genetic mutation and clinical efficacy, gene expression and its regulation. Results: YSSXL showed obvious therapeutic effect in treating β thalassemia. Gene analysis revealed that it did not change the genetic mutatio n type, but could obviously increase hemoglobin, fetal hemoglobin (HbF), γ/(β+ γ) globin ratio, γ globin mRNA expression and GM CSF mRNA expression in patients, as well as the GM CSFmRMA in marrow of mice after 60 Co radia tion. Conclusion: YSSXL has a remarkable therapeutic effect on β tha lassemia, and its possible mechanism is its action in unlocking γ gene, in creasing the γ globin expression and enhancing HbF synthesis so as to compe nsate for the gene defect. This study has opened a new path for the treatment of β thalassemia with TCM.

关键词： nourishing Shen and supplementing marrow principle Shen producing marrow β-thalassemia gene analysis mRNA gene ex pression molecular mechanism

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

Impact of Ferritin Load on Gonadal Reserve among Regular Transfused β-thalassemia

引用

Open Journal of Blood Diseases 2017年第2期7卷 65-78页

作者： Hasnaa A. Abo-Elwafa Safa A. Hamid Mena M. Heshmat Zahra S. Ahmed Clinical Pathology Department Faculty of Medicine Sohag University Sohag Egypt Pediatric Department Faculty of Medicine Sohag University Sohag Egypt

Background: Iron overload in association with persistent anemia is responsible for endocrine dysfunction in β-thalassemia patients, blood transfusion combined with iron-chelation can modify life quality in these children, but they tend to suffer from delayed maturity and endocrine dysfunction. Aim: This study aims to correlate degree of hypogonadism to ferritin load in regular transfused β-thalassemia patients. Methods: It was carried out on 30 β-thalassemia major (TM) patients aged 12 to 18 years, puberty was assessed clinically, blood picture on Cell-Dyne 2700, ferritin level and pattern of FSH, LH, testosterone and estradiol before and after gonadotropin (GnRH) analogue stimulation test, they were determined on ARCHITECT ABBOTT system. Results: Twenty patients had not yet achieved puberty, FSH level was 1.45 ± 1.88 mIU/ml before (GnRH) analogue and 3.78 ± 4.19 mIU/ml after 4 hours of injection. LH level was 1.91 ± 4.79 mIU/ml before (GnRH) test, while after 4 hours it was 6.52 ± 7.50 mIU/ml, 88.24% of males had low serum testosterone level, 84.6% of girls had low serum estradiol level, FSH, LH, estradiol, testosterone before and after GNRH analogue were statistically insignificant, mean ferritin level was 3344.32 ± 1142.142 ng/ml, with insignificant correlation to hormonal pattern before and after GnRH therapy. Conclusion: Iron overload and hypogonadism are the presenting data in this study, insignificant correlation between ferritin level and hormonal reserve pattern, there may be another etiology in pathophysiology of low gonadal reserve such as severe anemia, chronic disease and may be genetic predisposition underlying susceptibility to iron toxicity, which need further investigations.

关键词： Ferritin β-thalassemia Hypogonadism

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

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：