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Targeted core-shell nanoparticles for precise CTCF gene insert in treatment of metastatic breast cancer

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Bioactive Materials 2022年第5期7卷 1-14页

作者： Jialun Duan chunjie bao Ying Xie Haitao Guo Yixuan Liu Jianwei Li Rui Liu Peishan Li Jing Bai Yan Yan Limin Mu Xueqi Li Guiling Wang Wanliang Lu State Key Laboratory of Natural and Biomimetic Drugs Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery SystemsAnd School of Pharmaceutical SciencesPeking UniversityBeijing100191China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing100875China

Clustered regularly interspaced short palindromic repeats(CRISPR)technology emerges a remarkable potential for cure of refractory cancer like metastatic breast ***,how to efficiently deliver the CRISPR system with non-viral carrier remains a major issue to be ***,we report a kind of targeted core-shell nanoparticles(NPs)carrying dual plasmids(pHR-pCas9)for precise CCCTC-binding factor(CTCF)gene insert to circumvent metastatic breast *** targeted core-shell NPs carrying pHR-pCas9 can accomplishγGTP-mediated cellular uptake and endosomal escape,facilitate the precise insert and stable expression of CTCF gene,inhibit the migration,metastasis,and colonization of metastatic breast cancer ***,the finding further reveals that the inhibitory mechanism of metastasis could be associated with up-regulating CTCF protein,followed by down-regulating stomatin(STOM)*** study offers a universal nanostrategy enabling the robust non-viral delivery of gene-editing system for treatment of severe illness.

关键词： Core-shell nanoparticles Non-viral gene delivery Precise gene editing CTCF Metastatic breast cancer

Gene engineered exosome reverses T cell exhaustion in cancer immunotherapy

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Bioactive Materials 2024年第4期34卷 466-481页

作者： Peishan Li Ying Xie Jinling Wang chunjie bao Jialun Duan Yixuan Liu Qian Luo Jiarui Xu Yuxin Ren Min Jiang Jianwei Li Haitao Guo Huihui Zhao Guiling Wang Yanqin Liang Wanliang Lu State Key Laboratory of Natural and Biomimetic Drugs Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery SystemsSchool of Pharmaceutical SciencesPeking UniversityBeijing100191China Modern Research Center for Traditional Chinese Medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing100029China Beijing Institute of Collaborative Innovation Beijing100044China

Cancer patients by immune checkpoint therapy have achieved long-term remission,with no recurrence of clinical symptoms of cancer for many ***,more than half of cancer patients are not responsive to this therapy due to immune ***,we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod(PD1-Imi Exo)for boosting response of cancer immune checkpoint blockage *** results showed that PD1-Imi Exo had a vesicular round shape(approximately 139 nm),revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell,and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing *** mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8^(+)T cell with cancer cell,displaying a PD1/PDL1 immune checkpoint blockage effect,and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell,exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8^(+)T *** conclusion,the gene engineered exosome could be used for reversing T cell exhaustion in cancer *** study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy,preventing tumor recurrence or metastasis after surgery by rebuilding the patients’immunity,thus consolidating the overall prognosis.

关键词： Gene engineered exosomes T cell exhaustion PD1/PDL1 Imiquimod Cancer immunotherapy

中药活性成分作为药物递送纳米载体的研究进展

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中草药 2024年第16期55卷 5678-5691页

作者：韩静包纯洁段嘉伦南京中医药大学中药资源产业化与方剂创新药物国家地方联合工程中心江苏省中药资源产业化过程协同创新中心江苏省方剂高技术研究重点实验室江苏南京210023 南京中医药大学医学院江苏南京210023

随着对中药药效物质研究的不断深入,萜类、生物碱类、黄酮类、醌类、多糖等中药活性成分不仅具备显著的药理活性,而且展现出作为药物递送纳米载体的潜能。这些成分可以通过自组装、共组装或人工合成等形成胶束、聚合物、脂质体、纳米粒... 详细信息

随着对中药药效物质研究的不断深入,萜类、生物碱类、黄酮类、醌类、多糖等中药活性成分不仅具备显著的药理活性,而且展现出作为药物递送纳米载体的潜能。这些成分可以通过自组装、共组装或人工合成等形成胶束、聚合物、脂质体、纳米粒、水凝胶、乳液等多种药物递送纳米载体,从而提高药效、改善药性、实现药物共递释、减少不良反应。通过对近年来中药活性成分作为纳米载体材料在药物递送系统中的应用进行总结,分析了这些化合物形成药物递送纳米载体的机制,并展望了中药活性成分作为纳米载体材料在药物递送系统领域的发展潜力。有助于为中药活性成分实现“药辅合一”开辟新的研究方向,为中药现代化提供新的研究热点。

关键词：中药活性成分药物递送纳米载体药辅合一自组装中药制剂甘草酸人参皂苷喜树碱葛根素白及多糖

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基于响应面优化的结构有限元模型修正

北京航空航天大学学报 2014年第7期40卷 927-933页

作者：鲍诺王春洁北京航空航天大学机械工程及自动化学院北京100191

针对结构有限元分析中模型精度低的问题,提出了响应面优化的模型修正方法.利用优化拉丁方试验设计样本点,F值检验筛选出修正参数构造不完全4阶多项式响应面并检验响应面有效性.引入遗传算法以响应面计算值与试验值的残差为目标来优化修... 详细信息

针对结构有限元分析中模型精度低的问题,提出了响应面优化的模型修正方法.利用优化拉丁方试验设计样本点,F值检验筛选出修正参数构造不完全4阶多项式响应面并检验响应面有效性.引入遗传算法以响应面计算值与试验值的残差为目标来优化修正参数,将修正值代入初始模型中得到修正模型.三自由度系统数值算例,验证了模型中参数准确、参数不存在和参数有误差3种工况下,响应面优化方法的模型修正能力.以GARTEUR飞机模型为对象,筛选显著性参数进行模型修正,结果表明修正后模型不但在修正频段和预测频段具有良好的复现和预测能力,还能预测结构局部修改后的频率,证实了经过参数筛选后响应面优化的模型修正有效性.

关键词：试验设计参数筛选响应面模型修正模态频率遗传算法

Themis suppresses the effector function of CD8^(+)T cells in acute viral infection

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Cellular & Molecular Immunology 2023年第5期20卷 512-524页

作者： Jian Tang Xian Jia Jian Li Junchen Dong Jiayu Wang Wanyun Li Yuzhen Zhu Yanyan Hu Bowen Hou chunjie Lin Yu Cong Tong Ren Changsheng Yan Hongying Yang Qian Lai Haiping Zheng Yuzhou bao Namrata Gautam Hong-Rui Wang Bing Xu Xiao Lei Chen Qing Li Nicholas R.J.Gascoigne Guo Fu State Key Laboratory of Cellular Stress Biology School of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamenChina School of Life Sciences Xiamen UniversityXiamenChina Immunology Translational Research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Hematology The First Affiliated Hospital and Institute of HematologySchool of MedicineXiamen UniversityXiamenChina Cancer Research Center of Xiamen University XiamenChina

CD8^(+)T cells play a central role in antiviral immune *** infection,naive CD8^(+)T cells differentiate into effector cells to eliminate virus-infected cells,and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is *** extensively investigated,the underlying mechanisms of CD+T-cell differentiation remain incompletely *** is a T-cell-specific protein that plays critical roles in T-cell *** studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8^(+)T-cell homeostasis,cytokine responsiveness,and antibacterial *** this study,we used LCMV Armstrong infection as a probe to explore the role of Themis in viral *** found that preexisting CD8^(+)T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout *** analyses showed that in the primary immune response,Themis deficiency promoted the differentiation of CD8^(+)effector cells and increased their TNF and IFNy ***,Themis deficiency impaired memory precursor cell(MPEC)differentiation but promoted short-lived effector cell(SLEC)*** deficiency also enhanced effector cytokine production in memory CD8^(+)T cells while impairing central memory CD8^(+)T-cell ***,we found that Themis mediates PD-1 expression and its signaling in effector CD8^(+)T cells,which explains the elevated cytokine production in these cells when Themis is disrupted.

关键词： Themis Effector T cell CD8 T-cell differentiation Cytokine LCMV

富血小板纤维蛋白在下颌第三磨牙拔除术的应用系统评价与Meta分析

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华西口腔医学杂志 2021年第5期39卷 605-611页

作者：包明哲刘伟余树容门乙韩波李春洁口腔疾病研究国家重点实验室国家口腔疾病临床医学研究中心四川大学华西口腔医院头颈肿瘤外科成都610041 西南医科大学附属中医医院口腔科泸州646000

目的通过系统评价及Meta分析的方法评估下颌第三磨牙拔除术中使用富血小板纤维蛋白(PRF)的有效性,为缓解术后并发症提供建议。方法对Pubmed、EMBASE、Web of Science和中国生物医学文献数据库针对在下颌第三磨牙术中使用PRF的临床随机... 详细信息

目的通过系统评价及Meta分析的方法评估下颌第三磨牙拔除术中使用富血小板纤维蛋白(PRF)的有效性,为缓解术后并发症提供建议。方法对Pubmed、EMBASE、Web of Science和中国生物医学文献数据库针对在下颌第三磨牙术中使用PRF的临床随机对照试验进行电子检索,检索时间截至2020年2月。评价者使用Cochrane协作网推荐的标准对纳入文献进行偏倚风险评价并提取数据。运用RevMan 5.3和STATA 13.0进行Meta分析。结果共纳入21篇研究,包括991位拔除下颌第三磨牙患者。分析结果表明,局部应用PRF可以有效减轻拔牙术后疼痛[MD=-12.06,95%CI(-21.42,-2.71),P=0.01],降低拔牙后肿胀程度[MD=-1.42,95%CI(-2.41,-0.44),P=0.005],促进软组织愈合[MD=0.66,95%CI(0.34,0.99),P0.05)。结论目前有限的临床证据显示,下颌第三磨牙拔除术后使用PRF可以改善疼痛、肿胀、张口受限,减少干槽症的发生并促进软组织愈合。但是其对于骨愈合的影响需要进一步进行大规模的随机对照试验并统一测量标准后进行分析。

关键词：富血小板纤维蛋白下颌第三磨牙拔除术 Meta分析系统评价

福建紫金山矿田晚中生代英安玢岩形成时代及其成矿意义

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大地构造与成矿学 2012年第2期36卷 284-292页

作者：胡春杰黄文婷包志伟梁华英王春龙中国科学院广州地球化学研究所广东广州510640 中国科学院研究生院北京100049

福建紫金山Cu-Mo-Au-Ag多金属矿田是一个完整的斑岩-浅成低温热液矿床成矿体系。英安玢岩主要分布在紫金山Au-Cu矿床内火山机构及其附近,与高品位Au-Cu矿体空间上联系密切,是矿田内火山-侵入岩浆过程的一个重要环节。采自矿区的两个英... 详细信息

福建紫金山Cu-Mo-Au-Ag多金属矿田是一个完整的斑岩-浅成低温热液矿床成矿体系。英安玢岩主要分布在紫金山Au-Cu矿床内火山机构及其附近,与高品位Au-Cu矿体空间上联系密切,是矿田内火山-侵入岩浆过程的一个重要环节。采自矿区的两个英安玢岩样品LA-ICP-MS锆石U-Pb定年结果分别为(105.0±0.7)Ma(MSWD=0.83)和(105.0±2.2)Ma(MSWD=1.70),其形成时代与区内Mo-Cu矿化的萝卜岭和四方岩体形成时代相近。三个岩体形成时代及地球化学特征的相似性表明它们应为同源岩浆演化的产物,它们均具有较高的锆石Ce4+/Ce3+值,即岩浆体系具有较高的氧逸度,与区内斑岩成矿体系巨量金属堆积的地质事实相一致。英安玢岩的精确定年表明,紫金山Cu-Au矿与萝卜岭Mo-Cu矿及四方岩体有关的Mo矿床为同一斑岩成矿体系的产物。

关键词：年代学英安玢岩锆石Ce4+/Ce3+ 氧逸度紫金山矿田