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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Entries
Topic Review
Molecular Pathways Involved in the Regulation of BCBM
Brain metastasis is one of the major reasons of death in breast cancer (BC) patients, significantly affecting the quality of life, physical activity, and interdependence on several individuals. The tendency to develop breast cancer brain metastases (BCBMs) differs by the BC subtype, varying from almost half with triple-negative breast cancer (TNBC) (HER2− ER− PR−), one-third with HER2+ (human epidermal growth factor receptor 2-positive, and around one-tenth with luminal subclass (ER+ (estrogen positive) or PR+ (progesterone positive)) breast cancer. 
  • 857
  • 29 Dec 2022
Topic Review
RONS and Myokines in Skeletal Muscle Glucose Uptake
The skeletal muscle is the largest organ in the body that performs different functions, including those related to the movement of the body such as stability, equilibrium, and locomotion; vital functions such as breathing; and those associated with the maintenance of metabolic homeostasis, in which the generation and expenditure of energy and heat production are critical. The adequate interplay of these functions leads to the maintenance of life in organisms. Glucose is essential in metabolism since it is one of the main substrates that produces ATP, the key molecule that transfers energy during chemical reactions in organisms. To produce ATP, glucose needs to be transported from the extracellular space into the cytosol of the cell. This process is called glucose uptake, and it is critical in skeletal muscle since it provides enough glucose to the cell to produce ATP and satisfy the high demand for energy of the skeletal muscle. Glucose uptake in skeletal muscle tissue is a process mainly regulated by insulin, which is a hormone synthesized in the pancreas and released into the blood stream, where it is transported until it binds to specific insulin receptors that are anchored at the plasma membrane of skeletal muscle cells.
  • 858
  • 23 Dec 2022
Topic Review
Non-Invasive Pulsatile Shear Stress Modifies Endothelial Activation
The luminal surface of all the vasculature and the heart is lined by endothelial cells (EC), encompassing more than 5000 m2. Furthermore, the response of EC to external signals and the synthesis and production of various mediators is heterogeneous and adaptive based on location and signals. EC membranes are the sensing mechanism, responsive to mechanical (shear stress) and biochemical signaling (chemosensor). EC output is important for blood fluidity, coagulation, vasoreactivity, vasculogenesis, barrier function, and inflammation. Endothelial cell activation is the process by which EC changes from a quiescent cell phenotype, which maintains cellular integrity, antithrombotic, and anti-inflammatory properties, to a prothrombotic, pro-inflammatory, and permeable phenotype, also at the site of injury or infection, involved in repair and leukocyte trafficking. Endothelial activation is triggered by a multitude of stimuli that include inflammatory cytokines (interleukins, tumor necrosis factor, and interferon-γ), bacterial endotoxins, and pattern recognition receptor activation (PRR) after recognition of pathogen-associated molecular patterns (PAMP) or damage-associated molecular patterns (DAMP). Pathological activation of EC leads to increased vascular permeability, thrombosis, and an uncontrolled inflammatory response leading to endothelial dysfunction; the latter can be contained at the local level or participate in a more profound systemic response leading to multiorgan dysfunction and death.
  • 982
  • 06 Dec 2022
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.
  • 910
  • 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.
  • 663
  • 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.
  • 920
  • 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. 
  • 769
  • 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.
  • 718
  • 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.
  • 1.8K
  • 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. 
  • 655
  • 20 Apr 2022
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