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相关概念视频

Types of Toxins01:36

Types of Toxins

3.6K
Humans continually engage with an environment rich in potentially harmful chemicals. These are introduced to our bodies through inhalation, ingestion, or skin contact. These chemicals exist in various forms, such as air and environmental pollutants, agricultural chemicals, organic solvents, and heavy metals.
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
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Toxic Reactions: Overview01:26

Toxic Reactions: Overview

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When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
4.1K
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

379
Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
379
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

271
In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
271
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

151
Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
151
Toxicity Testing in Animals01:23

Toxicity Testing in Animals

200
Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...
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相关实验视频

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Isolation of High-density Lipoproteins for Non-coding Small RNA Quantification
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单颗粒光谱染色学揭示了脂质纳米粒子中异质RNA负载和大小相关性.

Sixuan Li1,2, Yizong Hu1,3,4, Jinghan Lin1,4,5

  • 1Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, United States.

ACS nano
|June 5, 2024
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概括

研究人员开发了一种新方法来分析脂质纳米粒子 (LNP) 用于RNA治疗. 这种技术揭示了LNP组成和RNA负载的显著异质性,为LNP组装提供了关键的见解.

关键词:
组成异质性的异质性.脂质纳米颗粒的使用方法多参数表征的多参数表征.纳米粒子色谱学 纳米粒子色谱学纳米粒子的有效载荷单粒子光谱学是一种单粒子光谱技术.

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A Quantitative Fluorescence Microscopy-based Single Liposome Assay for Detecting the Compositional Inhomogeneity Between Individual Liposomes
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科学领域:

  • 生物技术是生物技术.
  • 纳米技术纳米技术
  • 制药科学 制药科学

背景情况:

  • 脂质纳米粒子 (LNP) 是RNA疗法的关键传递系统.
  • 以前的研究经常假设LNP种群,负载和组成的均性.
  • 由于缺乏合适的工具,在单个粒子水平上描述LNP异质性一直是具有挑战性的.

研究的目的:

  • 开发一种可通用的策略来剖析多组件LNP组件的复杂性.
  • 创建一个高通量平台,以在单个粒子层面上表征LNP的物理化学性质.
  • 调查LNP异质性,包括种群身份,大小,RNA负载和脂质组成.

主要方法:

  • 开发了一种综合光谱染色学方法.
  • 该平台将圆柱式照明共聚焦光谱 (CICS) 与单纳米粒子自由溶液水力学分离 (SN-FSHS) 结合起来.
  • 这种方法同时对LNP中的种群身份,水力动力学大小,RNA负载和脂质分布进行分析.

主要成果:

  • 该平台成功地在一个基准siRNA LNP配方中区分了七个不同的LNP种群.
  • 实现了大小分布和RNA负载水平在广泛范围内的定量表征.
  • 关键的是,组成-大小相关性得到解决,揭示了RNA包装密度和大小依赖负载的异质性.

结论:

  • 开发的SN-FSHS-CICS分析提供了对LNP异质性的关键见解.
  • 观察到RNA包装密度和大小依赖负载的显著变化.
  • 这些发现表明,动力学驱动的组装机制负责RNA LNP的形成.