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Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed. 相似文献
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应用拷贝数变异测序(copy number variation sequencing,CNV-seq)技术鉴别来源不明的胎儿标记染色体,明确其遗传物质的来源,并探讨此技术在产前诊断中的应用价值。讨论Pallister-Killian综合征(Pallister-Killian syndrome,PKS)的临床特征及遗传学特点,提高对此类罕见染色体疾病的认识。该病例因在妊娠中期超声发现胎儿异常而行羊水穿刺进行CNV-Seq检测,同时分析胎儿和父母的核型。羊水CNV-Seq结果示该样本12号染色体p13.33-p11.1处检测到拷贝数为3.5、片段大小为34.70 Mb的嵌合重复区域;羊水染色体核型结果为47,XY,+i(12)(p10)[58]/46,XX[42],综合上述结果考虑为PKS。通过结合超声结果,综合应用染色体G显带核型分析和CNV-seq技术能准确确认染色体异常片段来源,在产前有效诊断PKS患者。 相似文献
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Moncef Khairallah Padmamalini Mahendradas Andre Curi Sana Khochtali Emmett T. Cunningham Jr. 《Ocular immunology and inflammation》2019,27(2):219-228
Purpose: To review the systemic and ocular manifestations of specific emergent viral infectious diseases relevant to the ophthalmologist with particular emphasis on anterior uveitisMethods: Review of literature.Results: Arboviral diseases are among the most important emergent and resurgent human infections, occurring mostly in tropical and subtropical zones, but appearing in virtually all regions of the world as a result of climate change, travel, and globalization. Arboviral infections are transmitted to humans by the bite of hematophagous arthropods, mainly mosquitoes. Systemic disease may range from asymptomatic to life-threatening. A wide variety of ocular manifestations, including uveitis, has been reported in association with these emerging viral diseases. Numerous viruses other than arboviruses also have been recently recognized as a potential cause of uveitis.Conclusions: Proper clinical diagnosis of any emerging infectious disease is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. The diagnosis is usually confirmed by detection of virus-specific DNA or antivirus antibodies in serum. 相似文献
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目的 检测分析被诊断为X连锁视网膜色素变性(XLRP)的三个中国家系内的基因突变。设计 基因研究。研究对象 三个中国XLRP家系共27位受试者(其中18人为男性)。方法 由同一医生收集家系成员的详细临床资料并进行眼部检查,采集三个家系的先证者及有条件采血者的外周静脉血,提取基因组DNA。应用PCR技术扩增RPGR和RP2基因的全部外显子和内含子交界区序列,包括RPGR基因15号外显子开放阅读框,产物直接测序进行突变分析。主要指标 临床特征及基因测序结果。结果 基因筛查证实了两个RPGR基因的新型无义突变(c.1541C>G;p.S514X 和 c.2833G>T;p.E945X) 及一个错义突变(c.607G>C;p.A203P)。基因型-表型的相关性分析表明家系3患者在接近ORF15下游位置存在突变,这种突变导致视锥细胞功能的早期丧失。ORF15无义突变的女性携带者临床表型重,呈现出部分显性遗传的特点。结论 本研究证实了三种RPGR基因的新型突变,这一结果扩展了RPGR的突变谱及表型谱。 相似文献
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Xiaoyan Lu Isabelle R. Miousse Sandra V. Pirela Jodene K. Moore Stepan Melnyk 《Nanotoxicology》2016,10(5):629-639
Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs. 相似文献
8.
背景 呼吸道合胞病毒(RSV)毛细支气管炎易出现反复喘息,且下呼吸道分泌物中半胱氨酸白三烯(CysLTs)水平升高。而孟鲁司特是一种白三烯受体拮抗剂,关于其治疗RSV毛细支气管炎症状的研究相对较少。目的 探讨孟鲁司特改善婴幼儿RSV毛细支气管炎后症状及减轻反复喘息发作的有效性和安全性。方法 2015年6月-2017年6月连续纳入在潍坊市妇幼保健院出院的RSV毛细支气管炎患儿,随机分为治疗组、对照组。Ⅰ期,治疗组:口服孟鲁司特颗粒(4 mg)12周,1次/d;对照组:口服安慰剂12周,1次/d。对两组无症状天数、个人日记评分进行评估。随访9个月(Ⅱ期),观察Ⅰ+Ⅱ期反复喘息人数和医疗资源应用情况等。依据意向性分析(ITT)原则,应用全分析集(FAS)分析数据。结果 共纳入研究对象186例,治疗组92例,对照组94例。治疗组完成Ⅰ期研究的患儿为89例,对照组为90例;治疗组完成Ⅰ+Ⅱ期的患儿为84例,对照组为86例。治疗组平均依从性为97.8%(7 560/7 728),对照组平均依从性为97.4%(7 690/7 896),两组患儿平均依从性比较,差异无统计学意义(χ2=3.16,P=0.07)。在Ⅰ期研究期间,两组无症状天数、日间无症状天数、夜间无症状天数、个人日记评分比较,差异均无统计学意义(P>0.05)。在整个研究过程中(Ⅰ+Ⅱ期),治疗组RSV毛细支气管炎喘息复发人数少于对照组(P<0.05),治疗组喘息患儿出现2次及以上喘息比例低于对照组(χ2=5.14,P=0.02)。Ⅰ+Ⅱ期研究期间治疗组医疗资源应用人数、β-受体激动剂应用人数、糖皮质激素应用人数、住院人数低于对照组(P<0.05)。在事后亚组分析中,治疗组有湿疹史与父母哮喘史的患儿中无症状天数〔(49.7±20.2)、(51.3±20.9)d〕多于对照组〔(36.3±20.4)、(37.8±19.3)d〕(t=2.19,P=0.03;t=2.24,P=0.03)。整个研究过程中没有患儿因不良反应退出研究,两组间胃肠道紊乱、皮疹、转氨酶升高发生率比较,差异均无统计学意义(χ2=0.23,P=0.63;χ2=0.03,P=0.86;χ2=0.15,P=0.69)。结论 口服孟鲁司特(4 mg)12周不能改善RSV毛细支气管炎患儿呼吸道症状,但能降低患儿反复喘息发作次数。口服孟鲁司特(4 mg)有一定效果且安全。 相似文献
9.
Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes. Circulating tumour DNA (ctDNA) is the most comprehensively studied liquid biopsy analyte in blood and can provide insight into the molecular profile and biological characteristics of individual PDAC tumours, in real-time and in advance of traditional imaging modalities. This can pave the way for identification of new therapeutic targets, novel risk variants and markers of tumour response, to supplement diagnostic screening and provide enhanced scrutiny in treatment stratification. In the roadmap towards the application of precision medicine for clinical management in PDAC, ctDNA analyses may serve a leading role in streamlining candidate biomarkers for clinical integration. In this review, we highlight recent developments in the use of ctDNA-based liquid biopsies for PDAC and provide new insights into the technical, analytical and biological challenges that must be overcome for this potential to be realised. 相似文献
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ABSTRACTThis work collates data from the analysis of complex mixtures analysed in STRmix during routine no-suspect volume crime work. It interrogates the upload rate for these types of mixtures and which component of the profile has been able to be interpreted for upload. The number of profiles giving multiple uploads and the amount of replicate PCR analysis has been collated. 相似文献