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Topic Review
Microglia Purinoceptor P2Y6
The purinergic receptor P2Y6 is expressed in immune cells, including microglia that are implicated in neurological disorders. Its ligand, UDP, is a signaling molecule that can serve as a "find‐me" signal when released in significant quantities by damaged/dying cells. Binding of UDP by P2Y6R leads to the activation of different biochemical pathways, depending on the disease context and the pathological environment. Generally, P2Y6R stimulates phagocytosis. However, whether or not phagocytosis coincides with cell activation or secretion of pro-inflammatory cytokines, needs further investigations.  The current review aims to discuss various functions of P2Y6R in some CNS disorders. We present evidence that P2Y6R may have a detrimental or beneficial role in the nervous system, in the context of neurological pathologies, such as ischemic stroke, Alzheimer's disease, Parkinson's disease, radiation-induced brain injury, neuropathic pain.
  • 797
  • 27 Oct 2020
Topic Review
Pathophysiology of Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) encompasses a group of heterogeneous diseases that entail chronic, relapsing gastrointestinal tract inflammation of inexactly known etiology and pathogenesis. IBD is clinically classified as Crohn’s disease (CD) or ulcerative colitis (UC) based on symptoms, disease location, and histopathological characteristics.
  • 795
  • 28 Jan 2023
Topic Review
Tau Isoforms
Tau was first described as a natively unfolded microtubule-associated protein. In fact, its main function is to promote the assembly of microtubules and stabilize their structure. However, Tau proteins have a variety of other functions, which include maintaining the structural integrity of neurons, contributing to signal transmission between neurons, and axonal transport. Tau also plays a role in regulating myelination, iron homeostasis, and neurogenesis and may also support synaptic plasticity. Other roles attributed to Tau are gene expression regulation, DNA protection, genome stability, microRNA activity, RNA protection, RNA metabolism, and protein synthesis.
  • 793
  • 27 Dec 2022
Topic Review
Gain of Function Mutant p53 in Cancer
The tumor suppressor p53, encoded by the TP53 gene and known as “the guardian of the genome”, performs a variety of functions in cancer prevention.
  • 790
  • 17 Nov 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.
  • 788
  • 06 Dec 2022
Topic Review
Perineuronal Nets
During restricted time windows of postnatal life, called critical periods, neural circuits are highly plastic and are shaped by environmental stimuli. In several mammalian brain areas, from the cerebral cortex to the hippocampus and amygdala, the closure of the critical period is dependent on the formation of perineuronal nets (PNNs). PNNs are condensed aggregates of an extracellular matrix (ECM) enwrapping the cell body, dendrites, and axon initial segments of several neurons in the adult central nervous system (CNS). They represent one form of an ECM in the CNS, together with the ECM that is loosely distributed in the parenchyma, the ECM that constitutes the basal lamina (which separates the CNS tissue from meningeal and vascular tissues), and the ECM that is located at the nodes of Ranvier.
  • 788
  • 11 Mar 2021
Topic Review
Copy-number Variation
Copy number variation (CNV) is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals. Copy number variation is a type of structural variation: specifically, it is a type of duplication or deletion event that affects a considerable number of base pairs. Approximately two-thirds of the entire human genome may be composed of repeats and 4.8–9.5% of the human genome can be classified as copy number variations. In mammals, copy number variations play an important role in generating necessary variation in the population as well as disease phenotype. Copy number variations can be generally categorized into two main groups: short repeats and long repeats. However, there are no clear boundaries between the two groups and the classification depends on the nature of the loci of interest. Short repeats include mainly bi-nucleotide repeats (two repeating nucleotides e.g. A-C-A-C-A-C...) and tri-nucleotide repeats. Long repeats include repeats of entire genes. This classification based on size of the repeat is the most obvious type of classification as size is an important factor in examining the types of mechanisms that most likely gave rise to the repeats, hence the likely effects of these repeats on phenotype.
  • 787
  • 02 Nov 2022
Topic Review
Volumetric Muscle Loss Repair
Volumetric muscle loss (VML) is defined as a condition in which a large volume of skeletal muscle is lost due to physical insult. VML often results in a heightened immune response, resulting in significant long-term functional impairment. 
  • 784
  • 23 Sep 2021
Topic Review
Glial Cells in Physiological and Pathological States
Glial cells are the most abundant and widely distributed cells that maintain cerebral homeostasis in the central nervous system. They mainly include microglia, astrocytes, and the oligodendrocyte lineage cells. Moreover, glial cells may induce pathological changes, such as inflammatory responses, demyelination, and disruption of the blood–brain barrier, to regulate the occurrence and development of neurological diseases through various molecular mechanisms.
  • 784
  • 29 Aug 2022
Topic Review
Three-Dimensional Culture Systems
It is getting more and more clear that cancer cell culture models are switching from two-dimension to three-dimensional, in order to better reflect in vivo situations where tumor cells have to cope with a highly interactive three-dimensional microenvironment. Several such culture models have been reported, predominantly multicellular tumor spheroids (MCTS) and patient-derived tumor organoids (PDTO). These are used both to investigate fundamental aspects of cancer development and as test systems for innovative therapies against gastric cancer, the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The authors review the actual state of research in this field to provide an overview of the contribution of MCTS and PDTO, especially in the areas of molecular profiling, drug discovery, pathogen infection, and personalized medicine.
  • 784
  • 18 Feb 2021
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