Summary

Nitric oxide, a gaseous free radical, is one of the ten smallest molecules found in nature. NO regulates vascular relaxation, controls inflammation, and suppresses expression of pro-inflammatory mediators in mast cells, macrophages, and vascular smooth muscles. NO regulates blood flow and modulates platelet and leukocyte activation, adhesion, and aggregation. This Entry Collection aims to help advance our understanding of the role that NO plays in physiology and pharmacology, which may lead to applications against various diseases.

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Topic Review
Type-2 Diabetes Mellitus and Dementia
Dementia is reported to be common in those with type 2 diabetes mellitus. Type 2 diabetes contributes to common molecular mechanisms and an underlying pathology with dementia. Brain cells becoming resistant to insulin leads to elevated blood glucose levels, impaired synaptic plasticity, microglial overactivation, mitochondrial dysfunction, neuronal apoptosis, nutrient deprivation, TAU (Tubulin-Associated Unit) phosphorylation, and cholinergic dysfunction.
  • 620
  • 30 Nov 2022
Topic Review
Potential NCE to Target Epithelial-Mesenchymal Transition
Epithelial-mesenchymal transition (EMT) is initiated by EMT activating transcription factors (EMT-TFs), including SNAIL (SNAI1) and SLUG (SNAI2), the basic helix–loop–helix factors TWIST1 and TWIST2. As proven for SNAIL, TWIST, Zinc figure E-box binding homeobox 1 (ZEB1), and Zinc figure E-box binding homeobox 2 (ZEB2), these features can repress epithelial genes like the E-cadherin-producing CDH1 by binding to E-Box in their cognate promoter regions.
  • 417
  • 15 Nov 2022
Topic Review
Endothelial Nitric Oxide Synthase in Perivascular Adipose Tissue
Perivascular adipose tissue (PVAT) is a special type of ectopic fat depot that adheres to most vasculatures. PVAT has been shown to exert anticontractile effects on the blood vessels and confers protective effects against metabolic and cardiovascular diseases. PVAT plays a critical role in vascular homeostasis via secreting adipokine, hormones, and growth factors. Endothelial nitric oxide synthase (eNOS; also known as NOS3 or NOSIII) is well-known for its role in the generation of vasoprotective nitric oxide (NO). eNOS is primarily expressed, but not exclusively, in endothelial cells, while studies have identified its expression in both adipocytes and endothelial cells of PVAT. PVAT eNOS is an important player in the protective role of PVAT.
  • 616
  • 08 Aug 2022
Topic Review
Nanostructures for Breast Cancer Diagnosis
Breast cancer (BC) is a highly metastatic multifactorial disease with various histological and molecular subtypes. Due to recent advancements, the mortality rate in BC has improved over the past five decades. Detection and treatment of many cancers are now possible due to the application of nanomedicine in clinical practice. Nanomedicine products such as Doxil® and Abraxane® have already been extensively used for BC adjuvant therapy with favorable clinical outcomes. 
  • 452
  • 20 Jul 2022
Topic Review
Dietary Nitrate and the Maintenance of Oral Health
Nitrate (NO3) is the oxidative product of nitric oxide (NO) and nitrite (NO2). As soil content, NO3 is an essential substrate for all plant growth and provides, among other things, the nitrogen required for the synthesis of nitrogenous amino acids. It is taken up by the plant roots and originates either from the microbial decomposition of organic waste or from the activity of certain soil bacteria utilizing atmospheric nitrogen for the synthesis of ammonia, nitrite and nitrate. Since available nitrate is the limiting factor for plant growth, it is deliberately added to the soil in agricultural crop production in the form of nitrate-containing fertilizers. Although the role of the oral microbiota as a key element in the alternative formation of NO2 and NO from nitrate-rich foods has been known for many years, it is surprisingly only in recent years that the therapeutic and preventive prospects of a nitrate-rich diet have attracted the interest of dental researchers.
  • 472
  • 10 Jun 2022
Topic Review
Nitric Oxide Synthase
Nitric oxide synthase (NOS) plays important roles within the cardiovascular system in physiological states as well as in pathophysiologic and specific cardiovascular (CV) disease states, such as hypertension (HTN), arteriosclerosis, and cerebrovascular accidents.
  • 1.5K
  • 07 May 2022
Topic Review
NO in Viral Infections
Nitric oxide is a ubiquitous signaling radical that influences critical body functions. Its importance in the cardiovascular system and the innate immune response to bacterial and viral infections has been extensively investigated. The overproduction of NO is an early component of viral infections, including those affecting the respiratory tract. The production of high levels of NO is due to the overexpression of NO biosynthesis by inducible NO synthase (iNOS), which is involved in viral clearance. The development of NO-based antiviral therapies, particularly gaseous NO inhalation and NO-donors, has proven to be an excellent antiviral therapeutic strategy. 
  • 463
  • 20 Apr 2022
Topic Review
Redox-Regulation of α-Globin in Vascular Physiology
Interest in the structure, function, and evolutionary relations of circulating and intracellular globins dates back more than 60 years to the first determination of the three-dimensional structure of these proteins. Non-erythrocytic globins have been implicated in circulatory control through reactions that couple nitric oxide (NO) signaling with cellular oxygen availability and redox status. Small artery endothelial cells (ECs) express free α-globin, which causes vasoconstriction by degrading NO. This reaction converts reduced (Fe2+) α-globin to the oxidized (Fe3+) form, which is unstable, cytotoxic, and unable to degrade NO. Therefore, (Fe3+) α-globin must be stabilized and recycled to (Fe2+) α-globin to reinitiate the catalytic cycle. The molecular chaperone α-hemoglobin-stabilizing protein (AHSP) binds (Fe3+) α-globin to inhibit its degradation and facilitate its reduction. The mechanisms that reduce (Fe3+) α-globin in ECs are unknown, although endothelial nitric oxide synthase (eNOS) and cytochrome b5 reductase (CyB5R3) with cytochrome b5 type A (CyB5a) can reduce (Fe3+) α-globin in solution.
  • 529
  • 28 Jan 2022
Topic Review
Therapeutic Approaches Utilizing Macrophage-Derived iNOS/NO in Cancer
Nitric oxide and its production by iNOS is an established mechanism critical to tumor promotion or suppression. Macrophages have important roles in immunity, development, and progression of cancer and have a controversial role in pro-and anti-tumoral effects. The tumor microenvironment consists of tumor-associated macrophages (TAM), among other cell types that influence the fate of the growing tumor. Depending on the microenvironment and various cues, macrophages polarize into a continuum represented by the M1-like pro-inflammatory phenotype or the anti-inflammatory M2-like phenotype; these two are predominant, while there are subsets and intermediates. Manipulating their plasticity through programming or reprogramming of M2-like to M1-like phenotypes presents the opportunity to maximize tumoricidal defenses. The dual role of iNOS derived NO also influences TAM activity by repolarization to tumoricidal M1-type phenotype. Regulatory pathways and immunomodulation achieve this through miRNA that may inhibit the immunosuppressive tumor microenvironment.
  • 608
  • 07 Dec 2021
Topic Review
Endothelial Nitric Oxide Synthase
Endothelial function is largely based on endothelial nitric oxide synthase (eNOS) function and activity. Likewise, oxidative stress can lead to the loss of eNOS activity or even “uncoupling” of the enzyme by adverse regulation of well-defined “redox switches” in eNOS itself or up-/down-stream signaling molecules. 
  • 761
  • 01 Dec 2021
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