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相关概念视频

Peripheral Artery Disease III: Interprofessional Care01:27

Peripheral Artery Disease III: Interprofessional Care

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Peripheral Artery Disease (PAD) is characterized by narrowed arteries that diminish blood flow to the extremities. Effective management of PAD requires an interprofessional approach involving various healthcare professionals. The critical aspects of interprofessional care for PAD patients focus on risk factor modification, drug therapy, exercise therapy, nutrition therapy, critical limb ischemia care, and interventional radiology and surgical procedures.The primary treatment goal for PAD...
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Peptic ulcer disease, commonly called PUD, represents a multifaceted condition characterized by disruptions in the lining of the gastrointestinal (GI)  tract. Central to the protection of the gastrointestinal lining is the mucosal-bicarbonate barrier. This physiological defense mechanism is a formidable shield against the corrosive effects of gastric acid and pepsin secretion in the stomach. Its role is pivotal in maintaining the structural integrity of the stomach's inner lining.
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Peripheral Artery Disease I: Introduction01:30

Peripheral Artery Disease I: Introduction

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Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs but also impacts other areas, such as the arms, thereby impairing overall circulation and organ function.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty deposits inside the arterial...
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Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

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Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
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IP3/DAG Signaling Pathway01:11

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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
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Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
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小分子通过准PAD2来激活素化.

Xue Zhang1,2, Mengzhen Shen1,2, Huimin Zhu1,2

  • 1Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences
|October 1, 2023
PubMed
概括

研究人员发现,demethoxycurcumin (DMC) 通过向丁氨酸减弱酶2 (PAD2) 来激活蛋白质素化. 这一发现提供了一种新的化学方法来激活素化,这是一个涉及各种疾病的过程.

关键词:
在PAD2中使用PAD2.激活器激活器是什么素化是指素化.德梅托西库尔库明 (demethoxycurcumin) 是一种可靠的药物.

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科学领域:

  • 生物化学 生物化学
  • 分子生物学分子生物学
  • 药理学 药理学是指药理学的学科.

背景情况:

  • 蛋白质素化,是一种由基氨酸脱胺酶 (PAD) 酶催化的翻译后修饰,与许多病理状况有关.
  • 虽然存在众多的素化抑制剂,但激活剂仍然很少,限制了对PAD酶功能和治疗潜力的研究.

研究的目的:

  • 为了选激活蛋白质素化作用的小分子.
  • 为了确定参与激活的特定PAD酶.
  • 描述已识别的激活剂的作用机制.

主要方法:

  • 使用抗体对抗素化组合素H3 (cit-H3) 的查以检测素化激活剂.
  • 功能丧失测试以确定PAD酶要求.
  • 直接结合测定和点突变分析以确定相互作用部位.
  • 对DMC诱导的细胞变化的表型分析.

主要成果:

  • 确定了demethoxycurcumin (DMC) 作为蛋白质素化的一个强有力的激活剂.
  • 证实了PAD2是DMC介导的氨酸酶的重要酶.
  • DMC直接与PAD2结合,其残留物E352对于这种相互作用至关重要.
  • 治疗DMC诱导细胞亡和DNA损伤,与PAD2失调一致.

结论:

  • 这项研究提出了一种新的选化激活剂选策略.
  • 甲基库尔库为激活蛋白质素化和研究PAD2功能提供了一种化学工具.
  • 这些发现为探索调节蛋白素化调节的治疗潜力开辟了新的途径.