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
Rokumijiogan, Hachimijiogan and Bakumijiogan in Nephrectomized Rats
According to the underlying concepts of TCM(traditional Chinese medicine) theory, chronic kidney disease (CKD) is commonly regarded as caused by Qi deficiency and Yang deficiency due to Xieqi repletion. The basic treatment principle of TCM is Yang/Qi-replenishing and Xieqi-draining. 
  • 312
  • 19 Jun 2023
Topic Review
Integrins and Immune Cells in Cancer Immunology
Integrins, a superfamily of cell adhesion receptors, bind to extracellular matrix (ECM) ligands and cell surface ligands to mediate physiological activities. Integrins are composed of a transmembrane α subunit and β subunit, with 18 α subunits and 8 β subunits currently known, constituting 24 heterodimers in humans that are divided into four categories: RGD receptors, leucocyte-specific receptors, collagen receptors, and laminin receptors.
  • 901
  • 12 Apr 2023
Topic Review
Cross-Talk of Gasotransmitters and Sphingolipid Signalling
Redox-active mediators are now appreciated as powerful molecules to regulate cellular dynamics such as viability, proliferation, migration, cell contraction, and relaxation, as well as gene expression under physiological and pathophysiological conditions. These molecules include the various reactive oxygen species (ROS), and the gasotransmitters nitric oxide (NO∙), carbon monoxide (CO), and hydrogen sulfide (H2S). For each of these molecules, direct targets have been identified which transmit the signal from the cellular redox state to a cellular response. There is a cross-regulation existing between the redox mediators and sphingolipid molecules that have a fundamental impact on a cell’s fate and organ function. 
  • 394
  • 03 Apr 2023
Topic Review
Physiological Effects of Nitric Oxide on Cartilage
Nitric oxide (NO) is a small gaseous molecule that is widely distributed in the human body, and its synthesis is dependent on NO synthase (NOS). NO plays an important role in various physiological processes such as the regulation of blood volume and nerve conduction. 
  • 476
  • 27 Feb 2023
Topic Review
General Reactivity of Heme Proteins with Nitric Oxide
Heme proteins (or hemeproteins or hemoproteins) are a structurally and functionally diverse group of metalloproteins exhibiting the heme moiety—an iron-coordinated porphyrin ring—as the prosthetic group. Nitric oxide (NO) is biosynthesized endogenously by heme proteins named NO synthases (NOSs), which oxidize the guanidino group of L-arginine into L-citrulline and NO in the presence of oxygen (O2) and reduced nicotinamide-adenine-dinucleotide phosphate (NADPH). 
  • 603
  • 23 Feb 2023
Topic Review
Modulation of NOS Isoforms by Dietary Polyphenols
Nitric oxide (NO) plays several key roles in the functionality of an organism, and it is usually released in numerous organs and tissues. There are mainly three isoforms of the enzyme that produce NO starting from the metabolism of arginine, namely endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and neuronal nitric oxide synthase (nNOS). The expression and activity of these isoforms depends on the activation/deactivation of different signaling pathways at an intracellular level following different physiological and pathological stimuli. Compounds of natural origin such as polyphenols, which are obtainable through diet, have been widely studied in in vivo and in vitro investigations for their ability to induce or inhibit NO release, depending on the tissue. 
  • 662
  • 28 Jan 2023
Topic Review
Nitric Oxide in Different Cancer Types
Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. 
  • 484
  • 16 Jan 2023
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. 
  • 623
  • 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.
  • 643
  • 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.
  • 751
  • 06 Dec 2022
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