检索结果-南通市图书馆

Functional characterization of a novel somatic oncogenic mutation of PIK3CB

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

Signal Transduction and Targeted Therapy 2017年第1期2卷 1-9页

作者： Andrew D Whale Lucy Colman Letitia Lensun Helen L Rogers Stephen J Shuttleworth Karus therapeutics ltd. Genesis BuildingLibrary AvenueHarwell CampusOxfordshireUK

Class I phosphoinositide 3-kinase(PI3K)enzymes have attracted considerable attention as drug targets in cancer therapy over the last 20 *** signaling pathway triggered by class I PI3Ks is dysregulated in a range of tumor types,impacting cell proliferation,survival and *** oncogenic mutations of PIK3CA have previously been *** contrast,reports of PIK3CB mutations have been limited;however,in most cases,those that have been identified have been shown to be activating and *** functional characterization of a PIK3CB catalytic domain mutant,p110β^(E1051K),first discovered by others in castrateresistant prostate cancer(mCRPC),is outlined in this report;our data suggest that p110β^(E1051K)is a gain-of-function mutation,driving PI3K signaling,tumorigenic cell growth and *** cells expressing p110β^(E1051K)are sensitive to p110βinhibition;its characterization as an oncogenic driver adds to the rationale for targeting p110βand indicates a continuing need to further develop specific PI3K inhibitors for clinical development in cancer therapy.

关键词： PIK3CB PIK3CA characterization

An engineered xCas12i with high activity,high specificity,and broad PAM range

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

Protein & Cell 2023年第7期14卷 540-545页

作者： Hainan Zhang Xiangfeng Kong Mingxing Xue Jing Hu Zikang Wang Yinghui Wei Haoqiang Wang Jingxing Zhou Weihong Zhang Mengqiu Xu Xiaowen Shen Fengcai Yin Zhiyuan Ai Guangyan Huang Junhui Xia Xueqiong Song Hengbin Li Yuan Yuan Jinhui Li Na Zhong Meiling Zhang Yingsi Zhou Hui Yang HuiEdit therapeutics Co. Ltd.Shanghai 200120China HuiGene therapeutics Co. Ltd.Shanghai 200120China Center for Reproductive Medicine International Peace Maternity and Child Health HospitalInnovative Research Team of High-level Local Universities in ShanghaiSchool of MedicineShanghai Jiao Tong UniversityShanghai 200030China

Dear Editor,The clustered regularly interspaced short palindromic repeats-Cas(CRISPR-Cas)systems,including type II Cas9 and type V Cas12 systems,which serve in the adaptive immunity of prokaryotes against viruses,have been developed into genome-editing tools(Anzalone et al.,2020;Doudna,2020).Compared with type II systems,the type V systems including V-A to V-K showed more functional diversity(Yan et al.,2019).Amongst them,Cas12i has a relatively smaller size(1,033-1,093 aa),compared to SpCas9 and Cas12a,and has a 5'-TTN protospacer adjacent motif(PAM)preference(Yan et al.,2019).

关键词： high specificity

Construction of supramolecular nanofibers through electrostatic interaction between perylene and cholesterol derivatives

在线全文

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2014年第1期25卷 51-54页

作者： Min Han Guo-Cheng Wang Hong-Quan Duan Tasly R&D Institute Tasly Holding Group Co.Ltd. Tianjin Key Laboratory on Technologies Enabling Development of Clinical therapeutics and Diagnostics School of PharmacyTianjin Medical University

The self-assembly of cationic perylene diimide （PDI） and anionic cholesterol derivatives （CHOL） was conveniently achieved by the electrostatic attraction and π-π stacking interactions, exhibiting the weft-define... 详细信息

关键词： Perylene diimide Cholesterol Electrostatic attraction Supramolecular nanofibers

New nitinol endovascular stent-graft system for abdominal aortic aneurysm with finite element analysis and experimental verification

在线全文

学校读者我要写书评

暂无评论

Rare Metals 2019年第6期38卷 495-502页

作者： Xiao-Chen Zhou Fan Yang Xiao-Yan Gong Ming Zhao Yu-Feng Zheng Zhi-Li Sun Department of Materials Science and Engineering College of EngineeringPeking UniversityBeijing 100871China Beijing Percutek therapeutics Co. Ltd.Beijing 102600China Suzhou Innomed Medical Device Co. Ltd.Suzhou 215123China Schlumberger Technology Corporation HoustonTX 77054USA State Key Laboratory for Turbulence and Complex System College of EngineeringPeking UniversityBeijing 100871China

Abdominal aortic aneurysm(AAA) is one of the most common and catastrophic manifestations of the acute aortic syndrome that can be treated with endovascular aneurysm repair(EVAR) which requires a specially designed stent-graft *** this work, a self-expanding nickel–titanium(nitinol) stent-graft system is aiming at AAA using finite element analysis(FEA) methods to analyze both fatigue behaviors and radial *** on the systematic analysis of the parametric variations, a final stent-graft system was developed by the selection and arrangement of the individual stent components, targeting an optimal performance for the treatment of *** tests, animal tests and clinical trials were carried out to confirm the *** animal trials and clinical trials showed comparable curative effects with Medtronic Endurant stent-graft(SG) systems.

关键词： Nitinol Stent-graft system Abdominal aortic aneurysm Fatigue safety factor Radial force Finite element analysis

AAV-mediated gene therapies by miniature gene editing tools

在线全文

学校读者我要写书评

暂无评论

Science China Life Sciences 2024年第12期67卷 2540-2553页

作者： Xiangfeng Kong Tong Li Hui Yang Shanghai Institute of Materia Medica Chinese Academy of Sciences Institute of Neuroscience Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Huida Gene therapeutics Co. Ltd. Shanghai Center for Brain Science and Brain-Inspired Technology

The advent of CRISPR-Cas has revolutionized precise gene editing. While pioneering CRISPR nucleases like Cas9 and Cas12 generate targeted DNA double-strand breaks(DSB) for knockout or homology-directed repair, next generation CRISPR technologies enable gene editing without DNA DSB. Base editors directly convert bases, prime editors make diverse alterations, and dead Cas-regulator fusions allow nuanced control of gene expression, avoiding potentially risks like translocations. Meanwhile, the discovery of diminutive Cas12 orthologs and Obligate Mobile Element-Guided Activity(OMEGA) nucleases has overcome cargo limitations of adeno-associated viral vectors, expanding prospects for in vivo therapeutic delivery. Here, we review the ever-evolving landscape of cutting-edge gene editing tools, focusing on miniature Cas12 orthologs and OMEGA effectors amenable to single AAV packaging. We also summarize CRISPR therapies delivered using AAV vectors, discuss challenges such as efficiency and specificity, and look to the future of this transformative field of in vivo gene editing enabled by AAV vectors delivery.

关键词： gene therapy adeno-associated viruses (AAVs) genome editing miniature CRISPR-Cas Obligate Mobile Element-Guided Activity (OMEGA)

Programmable deaminase-free base editors for G-to-Y conversion by engineered glycosylase

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

National Science Review 2023年第8期10卷 78-87页

作者： Huawei Tong Nana Liu Yinghui Wei Yingsi Zhou Yun Li Danni Wu Ming Jin Shuna Cui Hengbin Li Guoling Li Jingxing Zhou Yuan Yuan Hainan Zhang Linyu Shi Xuan Yao Hui Yang HuidaGene therapeutics Co. Ltd. Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience and Fujian Key Laboratory of Molecular Neurology Fujian Medical University Institute of Neuroscience Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Shanghai Center for Brain Science and Brain-Inspired Intelligence

Current DNA base editors contain nuclease and DNA deaminase that enables deamination of cytosine(C)or adenine(A), but no method for guanine(G) or thymine(T) editing is available at present. Here we developed a deaminase-free glycosylase-based guanine base editor(gGBE) with G editing ability, by fusing Cas9 nickase with engineered N-methylpurine DNA glycosylase protein(MPG). By several rounds of MPG mutagenesis via unbiased and rational screening using an intron-split EGFP reporter, we demonstrated that gGBE with engineered MPG could increase G editing efficiency by more than 1500 ***, this gGBE exhibited high base editing efficiency(up to 81.2%) and high G-to-T or G-to-C(i.e. G-to-Y) conversion ratio(up to 0.95) in both cultured human cells and mouse embryos. Thus, we have provided a proof-of-concept of a new base editing approach by endowing the engineered DNA glycosylase the capability to selectively excise a new type of substrate.

关键词： glycosylase base excision repair base editor depurination deaminase-free transversion

Adenosine-treated bioprinted muscle constructs prolong cell survival and improve tissue formation

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Bio-Design and Manufacturing 2021年第3期4卷 441-451页

作者： Dongxu Ke Adam M.Jorgensen Sang J.Lee James J.Yoo Sean V.Murphy Wake Forest Institute for Regenerative Medicine Wake Forest School of MedicineWinston-SalemNCUSA Novaprint therapeutics Suzhou Co. LtdSuzhouJiangsuChina

It is crucial to maintaining the viability of biofabricated human-sized tissues to ensure their successful survival and function after *** is a purine nucleoside that has the function to suppress cellular metabolism and has been previously proposed as a method to prolong cell viability under *** this study,we optimized the dose concentration of adenosine for incorporation into bioprinted constructs to preserve long-term cell viability in *** results showed that muscle cells(C2C12)containing 6,7,or 8 mM adenosine maintained high cell viability for 20 days under hypoxic conditions(0.1%O2),whereas cells without adenosine treatment showed 100%cell death after 11 *** 20 days under hypoxic conditions,muscle cells treated with adenosine proliferated and differentiated when transferred to normoxic *** these adenosine concentrations,6 mM was picked as the optimized adenosine concentration for further investigations due to its most effective results on improving cell *** bioprinted muscle constructs containing adenosine(6 mM)maintained high cell viability for 11 days under hypoxic conditions,while the control constructs without adenosine had no live *** in vivo validation,the bioprinted constructs with adenosine implanted under the dorsal subcutaneous space in mice,showed the enhanced formation of muscle tissue with minimal central necrosis and apoptosis,when compared to the constructs without *** positive in vitro and in vivo results demonstrate that the use of adenosine is an effective approach to preventing the challenge of hypoxia-induced necrosis in bioprinted tissues for clinical translation.

关键词： Bioprinting Hypoxia Adenosine Cell viability In vivo

Development of the novel ACLY inhibitor 326E as a promising treatment for hypercholesterolemia

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2023年第2期13卷 739-753页

作者： Zhifu Xie Mei Zhang Qian Song Long Cheng Xinwen Zhang Gaolei Song Xinyu Sun Min Gu Chendong Zhou Yangming Zhang Kexin Zhu Jianpeng Yin Xiaoyan Chen Jingya Li Fajun Nan State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Burgeon therapeutics Co. Ltd.Shanghai 201203China Drug Discovery Shandong Laboratory Bohai Rim Advanced Research Institute for Drug DiscoveryYantai 264117China

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia,which results in atherosclerosis and cardiovascular disease(CVD).ATP-citrate lyase(ACLY)is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle(TCA cycle)to acetyl-CoA in the ***,ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo *** this study,we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor,and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC_(50)=5.31±1.2μmol/L in vitro.326E treatment reduced de novo lipogenesis,and increased cholesterol efflux in vitro and in vivo.326E was rapidly absorbed after oral administration,exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid(BA)used for *** 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of *** daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^(-/-)mice to a greater extent than that of BA *** together,our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

关键词： Hypercholesterolemia Atherosclerosis Liver ATP-Citrate lyase(ACLY) Lipogenesis Cholesterol efflux ACLY inhibitor

Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation

在线全文

学校读者我要写书评

暂无评论

Engineering 2019年第1期5卷 150-155页

作者： Yifei Cheng Yuhong Chen Chenhua Yan Yu Wang Xiangyu Zhao Yao Chen Wei Han Lanping Xu Xiaohui Zhang Kaiyan Liu Shasha Wang Lungji Chang Lei Xiao Xiaojun Huang Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Peking University Institute of Hematology Peking University People’s Hospital Beijing 100044 China Collaborative Innovation Center of Hematology Peking University Beijing 100084 China Shenzhen Geno-Immune Medical Institute Shenzhen 518057 China Innovative Cellular therapeutics Co. Ltd. Shanghai 201499 China

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.

关键词： Donor-derived CD19-targeted T cell infusion Hematopoietic stem cell transplantation B cell acute lymphoblastic leukemia Minimal residual disease