Chip

CHIP
  • 文章类型: Journal Article
    改进的专业知识和技术进步使复杂和高风险的经皮冠状动脉介入治疗(CHIP)在先前被认为无法手术或高风险的患者中的安全有效表现。机械循环支持(MCS)装置在经皮冠状动脉介入治疗(PCI)相关缺血期间稳定血流动力学中起着至关重要的作用,从而降低重大不良事件的风险,实现更彻底的血运重建。然而,在受保护的PCI中使用MCS设备并非没有风险,包括围手术期心肌梗死(MI),出血,和通路相关的并发症。尽管进行了大量的观察性研究,目前显著缺乏在各种CHIP方案中比较不同MCS器械并评估其长期安全性和有效性的随机临床试验.这篇综述旨在总结目前关于MCS设备在CHIP期间的益处的证据,为根据临床情况选择合适的设备提供实用指南,并强调未来试验需要解决的悬而未决的问题。
    Improved expertise and technological advancements have enabled the safe and effective performance of complex and high-risk-indicated percutaneous coronary intervention (CHIP) in patients previously considered inoperable or high-risk. Mechanical circulatory support (MCS) devices play a crucial role in stabilizing hemodynamics during percutaneous coronary intervention (PCI) -related ischemia, thereby reducing the risk of major adverse events and achieving a more complete revascularization. However, the use of MCS devices in protected PCI is not without risks, including peri-procedural myocardial infarction (MI), bleeding, and access-related complications. Despite numerous observational studies, there is a significant lack of randomized clinical trials comparing different MCS devices in various CHIP scenarios and evaluating their long-term safety and efficacy profiles. This review aims to summarize the current evidence regarding the benefits of MCS devices during CHIPs, offer a practical guide for selecting appropriate devices based on clinical scenarios, and highlight the unanswered questions that future trials need to address.
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  • 文章类型: Journal Article
    Biohacking是一个术语,用于描述人们为了改善自己的健康而改变自己的身体。这包括射频识别植入物的植入。这种无线通信技术已经融入我们的日常生活,就像使用非接触式支付和徽章开门一样。自1998年首次在人体中植入射频识别技术以来,这项技术的可能性急剧增加,被削减的人数正在增加。手似乎是植入这些芯片的最受欢迎的身体部位,因为它可以很容易地靠近阅读器放置。目前,植入通常不在医疗环境中进行。然而,将这些装置植入人体会导致并发症,如感染和肌腱磨损,相关的安全影响尚未得到广泛研究。这项审查的范围是告知手外科医生社区这些植入物的存在,为什么它们被使用,并就手部外科医生在安全植入这些设备和处理可能的并发症方面可能的未来作用展开辩论。
    Biohacking is a term used to describe people making changes to their bodies to improve their well-being. This includes the implantation of radiofrequency identification implants. This technology for wireless communication is already incorporated into our daily lives as in the use of contactless payment and badges to open doors. Since the first radiofrequency identification implantation in a human in 1998, the possibilities of this technology have dramatically increased, and the number of persons that have been chipped is growing. The hand seems to be the most popular body part to implant these chips because it can easily be positioned close to a reader. Currently, implantation is typically not performed in a medical environment. However, implantation of these devices in humans can result in complications, such as infection and tendon attrition, and the relevant safety implications have not been extensively studied. The scope of this review was to inform the hand surgeon community about the existence of these implants, why they are used, and to open the debate about the possible future role of the hand surgeon in safely implanting these devices and dealing with possible complications.
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  • 文章类型: Journal Article
    不确定潜能(CHIP)的克隆造血与许多不良健康结局有关。然而,需要进一步的研究来了解与CHIP亚型相关的关键基因和途径,评估芯片克隆如何随时间演变,并进一步推进功能表征和治疗研究。大型流行病学研究可以很好地解决这些问题,但通常会从参与者那里收集唾液而不是血液。使用靶向CHIP基因小组对来自94名研究参与者的配对的唾液和血液来源的DNA样本进行测序。分析了最频繁鉴定为携带CHIP相关变体的10个基因。与CHIP相关的十四种独特变体,10个DNMT3A,TP53中的两个和TET2中的两个被鉴定为变异等位基因分数(VAF)在0.02和0.2之间,变异深度≥5个读数。在血液和唾液来源的DNA样品中检测到11种这些CHIP相关变体。在血液中检测到三种变体,VAF>0.02,但在配对唾液样品中低于该阈值(VAF0.008-0.013)。唾液来源的DNA适用于检测CHIP相关变体。唾液可以提供具有成本效益的生物样本,既可以推进CHIP研究,又可以促进临床转化为风险预测等环境。精密预防,和治疗监测。
    Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with many adverse health outcomes. However, further research is required to understand the critical genes and pathways relevant to CHIP subtypes, evaluate how CHIP clones evolve with time, and further advance functional characterisation and therapeutic studies. Large epidemiological studies are well placed to address these questions but often collect saliva rather than blood from participants. Paired saliva- and blood-derived DNA samples from 94 study participants were sequenced using a targeted CHIP-gene panel. The ten genes most frequently identified to carry CHIP-associated variants were analysed. Fourteen unique variants associated with CHIP, ten in DNMT3A, two in TP53 and two in TET2, were identified with a variant allele fraction (VAF) between 0.02 and 0.2 and variant depth ≥ 5 reads. Eleven of these CHIP-associated variants were detected in both the blood- and saliva-derived DNA sample. Three variants were detected in blood with a VAF > 0.02 but fell below this threshold in the paired saliva sample (VAF 0.008-0.013). Saliva-derived DNA is suitable for detecting CHIP-associated variants. Saliva can offer a cost-effective biospecimen that could both advance CHIP research and facilitate clinical translation into settings such as risk prediction, precision prevention, and treatment monitoring.
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  • 文章类型: Journal Article
    转录因子(TF)基因敲除或敲除实验提供了对基因调控的综合下游效应。然而,区分主要直接效应和次要效应仍然具有挑战性。为了评估TF结合事件的直接影响,我们提出了在人多能干细胞(hPSC)中建立多西环素(Dox)诱导型CRISPRd系统的方案。我们描述了建立CRISPRd宿主hPSC的步骤,设计和制备单向导RNA(sgRNA)表达慢病毒载体,产生用sgRNA转导的CRISPRdhPSC,并通过染色质免疫沉淀(ChIP)-qPCR分析CRISPRdTF阻断效应。有关此协议的使用和执行的完整详细信息,请参考松井等。1.
    Transcription factor (TF) gene knockout or knockdown experiments provide comprehensive downstream effects on gene regulation. However, distinguishing primary direct effects from secondary effects remains challenging. To assess the direct effect of TF binding events, we present a protocol for establishing a doxycycline (Dox)-inducible CRISPRd system in human pluripotent stem cells (hPSCs). We describe the steps for establishing CRISPRd host hPSCs, designing and preparing single-guide RNA (sgRNA) expression lentivirus vectors, generating CRISPRd hPSCs transduced with sgRNAs, and analyzing CRISPRd TF-block effects by chromatin immunoprecipitation (ChIP)-qPCR. For complete details on the use and execution of this protocol, please refer to Matsui et al.1.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    克隆造血(CH),突变克隆的相对扩增,来自造血干细胞(HSC),具有获得性体细胞或细胞遗传学改变,可改善细胞适应性。患有CH的个体患血液病和非血液病的风险较高,比如心血管疾病,总体死亡率较高。最初被认为仅限于一小部分老年人,单细胞测序和生物信息学的最新进展表明,具有多个扩展突变克隆的CH在老年人群中普遍存在。就在几年前,人类生命周期的系统发育重建和新的敏感测序技术表明,CH可以在生命早期开始,几十年前,它被认为是可能的。这些研究还表明,通过异常炎症起作用的环境因素可能是促进克隆扩展和疾病进展的共同主题。然而,这种现象的许多方面仍有待阐明,确切的机制,特定于上下文的驱动程序,和克隆扩增的途径仍有待建立。这里,我们回顾了我们目前对驱动CH的细胞机制的理解,并特别关注促炎因子如何影响正常和突变的HSC命运以促进克隆选择.
    Clonal hematopoiesis (CH), the relative expansion of mutant clones, is derived from hematopoietic stem cells (HSCs) with acquired somatic or cytogenetic alterations that improve cellular fitness. Individuals with CH have a higher risk for hematological and non-hematological diseases, such as cardiovascular disease, and have an overall higher mortality rate. Originally thought to be restricted to a small fraction of elderly people, recent advances in single-cell sequencing and bioinformatics have revealed that CH with multiple expanded mutant clones is universal in the elderly population. Just a few years ago, phylogenetic reconstruction across the human lifespan and novel sensitive sequencing techniques showed that CH can start earlier in life, decades before it was thought possible. These studies also suggest that environmental factors acting through aberrant inflammation might be a common theme promoting clonal expansion and disease progression. However, numerous aspects of this phenomenon remain to be elucidated and the precise mechanisms, context-specific drivers, and pathways of clonal expansion remain to be established. Here, we review our current understanding of the cellular mechanisms driving CH and specifically focus on how pro-inflammatory factors affect normal and mutant HSC fates to promote clonal selection.
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  • 文章类型: Journal Article
    在生物医学领域,有效和非侵入性地分离靶细胞一直是核心挑战之一。光纤镊子提供对培养基中细胞的精确和非侵入性操作,并且可以很容易地与微流体系统集成。因此,本文研究了光纤镊子利用散射力操纵细胞的机理。我们使用平端单模光纤驱动和分选细胞,并基于T矩阵模型得出相应的散射力公式。开发了一种用于细胞分选的单模光学镊子系统,并构建了光流控实验平台,将光学系统与微流控芯片有效集成。芯片,具有扩展的跨通道设计,成功实现了酵母细胞(直径8~10μm)和聚苯乙烯微球(直径15~20μm)的连续分离,分选效率高达86%,并在大约90%的酵母细胞中保持活力。与其他分拣系统相比,该系统不需要标记,并且可以以较低的仪器成本实现具有细胞活力的连续分选。
    In the field of biomedicine, efficiently and non-invasively isolating target cells has always been one of the core challenges. Optical fiber tweezers offer precise and non-invasive manipulation of cells within a medium and can be easily integrated with microfluidic systems. Therefore, this paper investigated the mechanism of cell manipulation using scattering force with optical fiber tweezers. We employed flat-ended single-mode fiber to drive and sort cells and derived the corresponding scattering force formula based on the T-matrix model. A single-mode optical tweezers system for cell sorting was developed, and an optofluidic experimental platform was constructed that effectively integrates the optical system with microfluidic chips. The chip, featuring an expanded cross-channel design, successfully achieved continuous separation of yeast cells (8~10 µm in diameter) and polystyrene microspheres (15~20 µm in diameter), with a sorting efficiency of up to 86% and maintaining viability in approximately 90% of the yeast cells. Compared to other sorting systems, this system does not require labeling and can achieve continuous sorting with cell viability at a lower cost of instrumentation.
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  • 文章类型: Journal Article
    多发性硬化症(MS)是一种影响中枢神经系统的慢性炎症。它的特点是脱髓鞘,胶质增生,神经轴突损伤,和炎症。流行的理论表明,MS起源于针对中枢神经系统内人体自身抗原的免疫反应。
    这篇研究论文“芯片上的神经炎症”研究多发性硬化症的主要目的是增强我们对MS发展的理解,展示尖端技术的应用,并可能为治疗方法提供有价值的见解。
    在各种书目数据库中搜索了本叙事评论的可用文献,PubMed,NCBI,和许多其他医疗参考使用单独验证,预先规定的方法。除了芯片上神经炎症的开发和优化以及该领域的创新进展外,有关MS及其神经炎症发病机制的重要性的研究已经在这项研究中进行了综述,以更好地理解“神经炎症-多发性硬化症的芯片”。根据循证医学中心的建议,考虑了纳入研究的证据水平。
    一些研究表明,与通常使用的常规细胞培养方法(如Transwell培养系统)相比,脑芯片模型紧密模仿皮质脑组织。此外,这些研究清楚地表明,使用脑芯片的进一步研究有可能增强我们对血脑屏障(BBB)转运蛋白在正常和疾病状态下的分子机制和作用的理解.
    了解神经炎症过程对于建立新的MS治疗方法仍然至关重要。脑芯片的利用有望提高我们对涉及BBB转运蛋白的分子过程的理解,在正常和患病状态。需要进一步的研究,以提高芯片上神经炎症的性能和理解,因此旨在为所有CNS疾病提供更有效的治疗。
    UNASSIGNED: Multiple sclerosis (MS) is a chronic inflammatory condition that impacts the central nervous system. It is distinguished by processes like demyelination, gliosis, neuro-axonal harm, and inflammation. The prevailing theory suggests that MS originates from an immune response directed against the body\'s own antigens within the central nervous system.
    UNASSIGNED: The main aim of this research paper \"Neuroinflammation-on-a-Chip\" for studying multiple sclerosis is to enhance our comprehension of MS development, demonstrate the application of cutting-edge technology, and potentially provide valuable insights for therapeutic approaches.
    UNASSIGNED: The available literature for this Narrative Review was searched on various bibliographic databases, PubMed, NCBI, and many other medical references using an individually verified, prespecified approach. Studies regarding the significance of MS and its neuroinflammatory pathogenesis in addition to the development and optimization of neuroinflammatory-on-a-chip and the advancement in innovations in this field have been reviewed in this research for a better understanding of \"Neuroinflammation-on-a-chip for multiple sclerosis\". The level of evidence of the included studies was considered as per the Centre for Evidence-Based Medicine recommendations.
    UNASSIGNED: Several studies have indicated that the brain-chip model closely mimics cortical brain tissue compared to commonly used conventional cell culture methods like the Transwell culture system. Additionally, these studies have clearly demonstrated that further research using brain chips has the potential to enhance our understanding of the molecular mechanisms and roles of blood-brain barrier (BBB) transporters in both normal and disease conditions.
    UNASSIGNED: Understanding neuroinflammation processes remains essential to establish new MS treatments approaches. The utilization of brain chips promises to advance our understanding of the molecular processes involving BBB transporters, both in normal and diseased states. Further research needs to be addressed in order to enhance the performance and understanding of neuroinflammation on a chip, hence aiming to provide more effective treatments for all CNS diseases.
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  • 文章类型: Journal Article
    我们制作了一种微流控芯片(成骨细胞[OB]-破骨细胞[OC]芯片),可以调节OB和OC上清液的混合量,以研究不同上清液分布对成骨或破骨细胞生成的影响。计算机辅助设计用于由聚二甲基硅氧烷生产OB-OC芯片。组装压力控制器并正确地确定OB和OC上清液的不同混合物。分化后,将OB和OC上清液置于OB-OC芯片的上面板上,用于体外评估。然后,我们使用中室中的MC3T3-E1细胞测试了成骨的变化。我们观察到OB和OC上清液的75:25分布在成骨中最有效。然后,我们使用OB-OC混合上清液或单独的OB上清液(上清液比例分别为75:25或100:0)引发MC3T3-E1细胞的成骨分化。将这些细胞置于大鼠的颅骨缺损部位。显微计算机断层扫描和组织学分析确定以75:25的比例暴露于OB-OC上清液的组中的骨形成明显更高。在这项研究中,我们证明了OB-OC芯片评估OB和OC不同上清液分布的影响的适用性。我们观察到,最高的骨形成潜力是在用条件培养基处理的MC3T3-E1细胞中,具体地,OB-OC上清液的比例为75:25。
    We fabricated a microfluidic chip (osteoblast [OB]-osteoclast [OC] chip) that could regulate the mixture amounts of OB and OC supernatants to investigate the effect of different supernatant distributions on osteogenesis or osteoclastogenesis. Computer-aided design was used to produce an OB-OC chip from polydimethylsiloxane. A pressure controller was assembled and different blends of OB and OC supernatants were correctly determined. OB and OC supernatants were placed on the upper panels of the OB-OC chip after differentiation for an in vitro evaluation. We then tested the changes in osteogenesis using MC3T3-E1 cells in the middle chambers. We observed that a 75:25 distribution of OB and OC supernatants was the most potent in osteogenesis. We then primed the osteogenic differentiation of MC3T3-E1 cells using an OB-OC mixed supernatant or an OB supernatant alone (supernatant ratios of 75:25 or 100:0, respectively). These cells were placed on the calvarial defect sites of rats. Microcomputed tomography and histological analyses determined a significantly higher bone formation in the group exposed to the OB-OC supernatant at a ratio of 75:25. In this study, we demonstrate the applicability of an OB-OC chip to evaluate the effect of different supernatant distributions of OB and OC. We observed that the highest bone-forming potential was in MC3T3-E1 cells treated with conditioned media, specifically the OB-OC supernatant at a ratio of 75:25.
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  • 文章类型: Journal Article
    胰岛素/IGF信号(IIS)调节发育和代谢可塑性。胰岛素样肽表达和分泌的条件调节在不同环境中促进不同表型。然而,IIS也可以由其他了解较少的机制。例如,秀丽隐杆线虫中唯一已知的胰岛素/IGF受体的稳定性,DAF-2/INSR,受CHIP依赖性泛素化调节。chn-1/CHIP的破坏通过增加成人的DAF-2/INSR丰度和IIS活性来降低秀丽隐杆线虫的寿命。同样,泛素化位点的突变导致daf-2(gk390525)在成人中显示功能获得表型。然而,我们表明该等位基因在幼虫中表现出功能丧失的表型,在开发过程中,它对IIS活动的影响从负面转变为正面。相比之下,等位基因在高温下培养的幼虫中起着功能增益的作用,抑制温度依赖性道尔形成。chn-1/CHIP的破坏导致饥饿的L1幼虫的IIS活性增加,不同于DAF-2(gk390525)。CHN-1/CHIP在多个位点泛素化DAF-2/INSR。这些结果表明,与IIS负调控功能相关的位点在幼虫和成虫中有所不同,在不同的温度下,以营养依赖的方式,揭示IIS调节的附加层。
    类胰岛素信号在帮助动物适应不同的环境条件中起着至关重要的作用。胰岛素分子丰度的差异驱动胰岛素信号的差异,影响生长,新陈代谢,和对压力条件的抵抗力。在线虫线虫中的先前工作表明,胰岛素受体的靶向降解也调节胰岛素信号传导。我们在这里表明,这个过程受发育阶段的影响,营养可用性,和温度,揭示了胰岛素样信号在这个有价值的动物模型中被调节的其他方式。
    Insulin/IGF signaling (IIS) regulates developmental and metabolic plasticity. Conditional regulation of insulin-like peptide expression and secretion promotes different phenotypes in different environments. However, IIS can also be regulated by other, less-understood mechanisms. For example, stability of the only known insulin/IGF receptor in C. elegans, DAF-2/INSR, is regulated by CHIP-dependent ubiquitination. Disruption of chn-1/CHIP reduces longevity in C. elegans by increasing DAF-2/INSR abundance and IIS activity in adults. Likewise, mutation of a ubiquitination site causes daf-2(gk390525) to display gain-of-function phenotypes in adults. However, we show that this allele displays loss-of-function phenotypes in larvae, and that its effect on IIS activity transitions from negative to positive during development. In contrast, the allele acts like a gain-of-function in larvae cultured at high temperature, inhibiting temperature-dependent dauer formation. Disruption of chn-1/CHIP causes an increase in IIS activity in starved L1 larvae, unlike daf-2(gk390525). CHN-1/CHIP ubiquitinates DAF-2/INSR at multiple sites. These results suggest that the sites that are functionally relevant to negative regulation of IIS vary in larvae and adults, at different temperatures, and in nutrient-dependent fashion, revealing additional layers of IIS regulation.
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