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Blood direct PCR: impact of CYP2C19 and CYP4F2 variants for bleeding prediction in ST-elevation myocardial infarction patients with ticagrelor. 血液直接PCR: CYP2C19和CYP4F2变异对替格瑞洛st段抬高型心肌梗死患者出血预测的影响
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-05-01 Epub Date: 2022-02-17 DOI: 10.2217/pme-2021-0152
Vacis Tatarunas, Ali Aldujeli, Zemyna Kurnickaite, Laurynas Maciulevicius, Marius Burkanas, Jonas Venius, Ieva Ciapiene, Vilius Skipskis, Rita Norvilaite, Agne Giedraitiene, Ramunas Unikas, Giedre Baksyte, Olivija Gustiene, Gintare Sakalyte, Vaiva Lesauskaite

Aims: The goals of this study were to develop a new technique that could pave the way for a quicker determination of CYP4F2 rs3093135 and CYP2C19 rs4244285 variants directly from a patient's blood and to attempt to apply this technique in clinical practice. Patients & methods: The study included 144 consecutive patients admitted with ST elevation myocardial infarction. A blood-direct PCR and real-time PCR were used to detect variants of interest. Results & conclusion: Patients with bleeding events had the CYP2C19 GG (*1*1) variant more frequently than patients without bleeding events. The CYP4F2 TT variant was more frequently detected in patients with bleeding events 3 months after hospitalization.

目的:本研究的目的是开发一种新技术,为直接从患者血液中更快地测定CYP4F2 rs3093135和CYP2C19 rs4244285变异铺平道路,并尝试将该技术应用于临床实践。患者与方法:研究纳入144例ST段抬高型心肌梗死患者。采用血液直接PCR和实时PCR检测感兴趣的变异。结果与结论:有出血事件的患者CYP2C19 GG(*1*1)变异发生率高于无出血事件的患者。CYP4F2 TT变异更常见于住院后3个月出血事件的患者。
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引用次数: 1
SKA3, negatively regulated by miR-128-3p, promotes the progression of non-small-cell lung cancer. 受miR-128-3p负调控的SKA3促进非小细胞肺癌的进展。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-05-01 Epub Date: 2021-09-17 DOI: 10.2217/pme-2020-0095
Linlin Xie, Shaofei Cheng, Zhengyang Fan, Hongyang Sang, Qianping Li, Song Wu
Aim: To investigate the effects of SKA3 on cell proliferation and metastasis in non-small-cell lung cancer (NSCLC) and its underlying mechanism. Methods: Immunohistochemistry was employed to analyze the expression of SKA3 in NSCLC. CCK-8 assay, EdU assay, Transwell assay and flow cytometry analysis were employed to assess cell proliferation, metastatic potential and apoptosis in vitro, respectively. A lung metastasis model was used to evaluate metastasis of NSCLC cells in vivo. A luciferase reporter gene assay was conducted to verify the targeting relationship. Results: SKA3 exhibited high expression in NSCLC tissues and cells. Overexpression of SKA3 remarkably accelerated cell proliferation and metastasis and suppressed apoptosis of NSCLC cells and promoted lung metastasis in a mouse model. miR-128-3p repressed SKA3 expression by targeting it. Conclusion: miR-128-3p inhibited the progression of NSCLC through targeting SKA3.
目的:探讨SKA3对非小细胞肺癌(NSCLC)细胞增殖和转移的影响及其机制。方法:采用免疫组化方法分析SKA3在NSCLC中的表达。分别采用CCK-8法、EdU法、Transwell法和流式细胞术检测体外细胞增殖、转移潜能和凋亡。采用肺转移模型评价非小细胞肺癌细胞的体内转移情况。荧光素酶报告基因测定验证了靶向关系。结果:SKA3在NSCLC组织和细胞中高表达。在小鼠模型中,SKA3过表达可显著加速细胞增殖和转移,抑制非小细胞肺癌细胞凋亡,促进肺转移。miR-128-3p通过靶向SKA3抑制其表达。结论:miR-128-3p通过靶向SKA3抑制NSCLC的进展。
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引用次数: 3
A precision medicine approach to stress testing using metabolomics and microribonucleic acids. 一种使用代谢组学和微小核糖核酸进行压力测试的精确医学方法。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-04-25 DOI: 10.2217/pme-2021-0021
A. Limkakeng, L. Rowlette, A. Hatch, A. Nixon, O. Ilkayeva, D. Corcoran, J. Modliszewski, S. M. Griffin, G. Ginsburg, D. Voora
Both transcriptomics and metabolomics hold promise for identifying acute coronary syndrome (ACS) but they have not been used in combination, nor have dynamic changes in levels been assessed as a diagnostic tool. We assessed integrated analysis of peripheral blood miRNA and metabolite analytes to distinguish patients with myocardial ischemia on cardiac stress testing. We isolated and quantified miRNA and metabolites before and after stress testing from seven patients with myocardial ischemia and 1:1 matched controls. The combined miRNA and metabolomic data were analyzed jointly in a supervised, dimension-reducing discriminant analysis. We implemented a baseline model (T0) and a stress-delta model. This novel integrative analysis of the baseline levels of metabolites and miRNA expression showed modest performance for distinguishing cases from controls. The stress-delta model showed worse performance. This pilot study shows potential for an integrated precision medicine approach to cardiac stress testing.
转录组学和代谢组学都有望识别急性冠状动脉综合征(ACS),但它们尚未联合使用,也没有将水平的动态变化作为诊断工具进行评估。我们评估了外周血miRNA和代谢产物分析的综合分析,以在心脏压力测试中区分心肌缺血患者。我们在压力测试前后从7名心肌缺血患者和1:1匹配的对照组中分离并定量了miRNA和代谢产物。在有监督的降维判别分析中,联合分析miRNA和代谢组学数据。我们实现了一个基线模型(T0)和一个应力增量模型。这项新的代谢产物和miRNA表达基线水平的综合分析显示,在区分病例和对照组方面表现平平。应力德尔塔模型表现出较差的性能。这项初步研究显示了一种综合精确医学方法用于心脏压力测试的潜力。
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引用次数: 1
Role of precision nutrition in improving military performance. 精确营养在提高军事性能中的作用。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-03-16 DOI: 10.2217/pme-2021-0120
Coimbatore Subburaj Thiruvenkataswamy, M. Appukutty, K. S. Vimaleswaran
Graphical abstract [Formula: see text] Role of precision nutrition in improving military performance.
图形摘要[公式:见正文]精确营养在提高军事性能中的作用。
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引用次数: 2
State-of-the-art knowledge on the regulation of advanced therapy medicinal products. 先进治疗药品监管方面的最新知识。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-03-16 DOI: 10.2217/pme-2021-0111
Patcharaphun Kidpun, Warit Ruanglertboon, R. Chalongsuk
Advanced therapy medicinal products (ATMPs) constitute therapeutic agents based on obtained cells, tissues or genes representing a novel treatment opportunity in medicine. In addition, ATMPs are administered into the cells or tissues of humans from the patient's own cells, donors, or genetically modified cells. Recently, the field of developing ATMPs has become a point of attention due to the clinical efficacy expected in defeating incurable diseases such as cancers and neurodegenerative disorders. Currently, there are two modes regarding the distribution of ATMPs. First, ATMPs that might be legally authorized for marketing. Second, the patients are able to access unapproved ATMPs through the hospital exemption (HE) or clinical practice program or through the compassionate use and expanded access program. The aim of this review is to discuss state-of-the-art knowledge on the regulation of ATMPs and provide regulatory recommendations.
高级治疗药物(ATMP)是基于获得的细胞、组织或基因的治疗剂,代表了医学中的新治疗机会。此外,ATMP是从患者自身的细胞、供体或转基因细胞给药到人类的细胞或组织中的。最近,由于在战胜癌症和神经退行性疾病等不治之症方面的临床疗效,开发ATMP的领域已成为人们关注的焦点。目前,ATM的分配有两种模式。首先,可能被合法授权进行营销的ATM。其次,患者可以通过医院豁免(HE)或临床实践计划,或通过同情使用和扩大访问计划,访问未经批准的ATM。本次审查的目的是讨论ATM监管的最新知识,并提供监管建议。
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引用次数: 1
How can we address the uncertainties regarding the potential clinical utility of polygenic score-based tests? 我们如何解决基于多基因评分的测试潜在临床效用的不确定性?
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-03-15 DOI: 10.2217/pme-2021-0148
S. Moorthie, A. Hall, Chantal Babb de Villiers, Joanna Janus, Tanya Brigden, Laura Blackburn, M. Kroese
As common low penetrance variants associated with diseases are uncovered, attempts continue to be made to harness this knowledge for improving healthcare. Polygenic scores have been developed as the mechanism by which knowledge of common variants can be used to investigate genetic contributions to disease risk. They serve as a biomarker to provide an estimate of the genetic liability for a particular disease. Discussion continues as to whether polygenic scores are a useful biomarker and their readiness for incorporation into clinical and public health practice. In this paper, we investigate the key challenges that need to be addressed, in the description and assessment of the clinical utility of polygenic score-based tests for use in clinical and public health practice.
随着与疾病相关的常见低外显率变异被发现,人们继续试图利用这一知识来改善医疗保健。多基因评分已经发展成为一种机制,通过这种机制,常见变异的知识可以用来研究遗传对疾病风险的影响。它们作为一种生物标志物,提供对特定疾病的遗传倾向性的估计。关于多基因评分是否是一种有用的生物标志物,以及它们是否适合用于临床和公共卫生实践的讨论仍在继续。在本文中,我们调查了在临床和公共卫生实践中使用的多基因评分测试的临床效用的描述和评估中需要解决的关键挑战。
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引用次数: 3
Exploring the usefulness of plasma level determination and pharmacogenetics for patients treated with clozapine. 探讨血浆水平测定和药物遗传学对氯氮平治疗患者的有用性。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-03-09 DOI: 10.2217/pme-2021-0029
Estela Sangüesa, Christine Cirujeda, Julia Concha, P. Padilla, C. García, M. Ribate
Aims: The aims of the present study were to assess the variance of plasma clozapine (CLZ) levels and to identify the influence of sociodemographic and pharmacogenetic factors on it and to introduce these tools in a clinical setting. Patients & methods: CLZ concentration was measured and genetic variants of CLZ pharmacokinetic and pharmacodynamic factors were assessed in 23 patients with psychotic disorders. Results: A significant association between mean concentration/dose ratio (C/D) and smoking status, age and weight were found. There was a significant difference in mean plasma CLZ levels and gender. The rs762551 AA genotype in smokers had a significantly lower C/D. Conclusion: In addition to classical factors, monitoring of plasma concentrations together with pharmacogenetics led to greater individualization of treatment.
目的:本研究的目的是评估血浆氯氮平(CLZ)水平的变化,确定社会人口统计学和药物遗传学因素对其的影响,并在临床环境中引入这些工具。患者和方法:测定23例精神病患者的CLZ浓度,并评估CLZ药代动力学和药效学因素的遗传变异。结果:平均浓度/剂量比(C/D)与吸烟状况、年龄和体重之间存在显著相关性。平均血浆CLZ水平和性别存在显著差异。吸烟者rs762551 AA基因型的C/D显著降低。结论:除经典因素外,监测血浆浓度和药物遗传学可提高治疗的个体化程度。
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引用次数: 3
Interindividual variability in diabetic patients' response to opium poppy: an overview of impressive factors. 糖尿病患者对罂粟反应的个体差异:令人印象深刻的因素概述。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-03-01 DOI: 10.2217/pme-2021-0107
Fatemeh Hendijani, Fatemeh Sadat Hosseini

Diabetic patients always seek alternative treatments to lower their blood glucose level efficiently, because antidiabetic drugs produce adverse effects and many patients experience reduced response after a treatment period. Opium poppy (Papaver somniferum) is frequently consumed by diabetic patients for reduction of blood glucose level. Scientific studies found controversial results in the investigation of the blood glucose-lowering effects of opium poppy. In this regard, we explored the antidiabetic effect of opium poppy more closely. The antidiabetic or antihyperglycemic effect of P. somniferum alkaloids were reviewed. Next, opioid receptors and their role in diabetes were explored. In the final part origins of interindividual variabilities in opioid receptors and metabolizing enzymes' functions including genetic and epigenetic factors were reviewed.

糖尿病患者总是寻求替代治疗来有效降低血糖水平,因为降糖药物会产生不良反应,许多患者在治疗一段时间后反应降低。罂粟(Papaver somniferum)常被糖尿病患者食用以降低血糖水平。科学研究在对罂粟降血糖效果的调查中发现了有争议的结果。在这方面,我们更密切地探讨了罂粟的抗糖尿病作用。本文综述了菟菟子生物碱的降糖、降血糖作用。接下来,探讨阿片受体及其在糖尿病中的作用。最后,综述了阿片受体和代谢酶功能的个体间变异的起源,包括遗传和表观遗传因素。
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引用次数: 0
Investigating underlying human immunity genes, implicated diseases and their relationship to COVID-19 研究潜在的人类免疫基因、相关疾病及其与新冠肺炎的关系
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-01-01 DOI: 10.2217/pme-2021-0132
Zeeshan Ahmed, E. G. Renart, Saman Zeeshan
Aim: A human immunogenetics variation study was conducted in samples collected from diverse COVID-19 populations. Materials & methods: Whole-genome and whole-exome sequencing (WGS/WES), data processing, analysis and visualization pipeline were applied to identify variants associated with genes of interest. Results: A total of 2886 mutations were found across the entire set of 13 genomes. Functional annotation of the gene variants revealed mutation type and protein change. Many variants were found to be biologically implicated in COVID-19. The involvement of these genes was also found in multiple other diseases. Conclusion: The analysis determined that ACE2, TMPRSS4, TMPRSS2, SLC6A20 and FYCOI had functional implications and TMPRSS4 was the gene most altered in virally infected patients.
目的:对收集自不同新冠肺炎人群的样本进行人体免疫遗传学变异研究。材料与方法:应用全基因组和全外显子组测序(WGS/WES)、数据处理、分析和可视化管道来识别与感兴趣基因相关的变体。结果:在整个13个基因组中共发现2886个突变。基因变体的功能注释揭示了突变类型和蛋白质变化。许多变异被发现与新冠肺炎有生物学意义。在其他多种疾病中也发现了这些基因的参与。结论:分析确定ACE2、TMPRSS4、TMPRSS2、SLC6A20和FYCOI具有功能意义,TMPRSS4是病毒感染患者中变化最大的基因。
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引用次数: 1
Interventional cardiologists' attitudes towards pharmacogenetic testing and impact on antiplatelet prescribing decisions. 介入心脏病专家对药物遗传学检测的态度及其对抗血小板处方决策的影响。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-01-01 Epub Date: 2021-12-09 DOI: 10.2217/pme-2021-0088
Glenda Hoffecker, Genevieve P Kanter, Yao Xu, William Matthai, Daniel M Kolansky, Jay Giri, Sony Tuteja

Aim: To determine if interventional cardiologists' knowledge and attitudes toward pharmacogenetic (PGx) testing influenced their antiplatelet prescribing decisions in response to CYP2C19 results. Materials & methods: Surveys were administered prior to participating in a randomized trial of CYP2C19 testing. Associations between baseline knowledge/attitudes and agreement with the genotype-guided antiplatelet recommendations were determined using multivariable logistic regression. Results: 50% believed that PGx testing would be valuable to predict medication toxicity or efficacy. 64% felt well informed about PGx testing and its therapeutic application. However, PGx experience, knowledge, nor attitudes were significantly associated with agreement to genotype-guided antiplatelet recommendations. Conclusion: Cardiologists' knowledge and attitudes were not associated with CYP2C19-guided antiplatelet prescribing, but larger studies should be done to confirm this finding.

目的:了解介入心脏病医师对药物遗传学(PGx)检测的知识和态度是否会影响其CYP2C19检测结果对抗血小板处方的影响。材料与方法:在参加CYP2C19检测的随机试验之前进行调查。使用多变量逻辑回归确定基线知识/态度与基因型指导抗血小板建议的一致性之间的关联。结果:50%的人认为PGx检测对预测药物毒性或疗效有价值。64%的人对PGx检测及其治疗应用知情。然而,PGx的经验、知识和态度与基因型指导抗血小板建议的一致性显著相关。结论:心脏病专家的知识和态度与cyp2c19指导的抗血小板处方无关,但需要进行更大规模的研究来证实这一发现。
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引用次数: 0
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Personalized medicine
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