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Topic Review
FAAH inhibitor URB597
Since the inhibition of fatty acid amide hydrolase (FAAH), the main catabolic enzyme of anandamide (AEA), may provide beneficial effects in mice model of Alzheimer’s disease (AD)-like pathology, we aimed at determining whether the FAAH inhibitor URB597 might target microglia polarization and alter the cytoskeleton reorganization induced by the amyloid-β peptide (Aβ). The morphological evaluation showed that Aβ treatment increased the surface area of BV-2 cells, which acquired a flat and polygonal morphology. URB597 treatment partially rescued the control phenotype of BV-2 cells when co-incubated with Aβ. Moreover, URB597 reduced both the increase of Rho protein activation in Aβ-treated BV-2 cells and the Aβ-induced migration of BV-2 cells, while an increase of Cdc42 protein activation was observed in all samples. URB597 also increased the number of BV-2 cells involved in phagocytosis. URB597 treatment induced the polarization of microglial cells towards an anti-inflammatory phenotype, as demonstrated by the decreased expression of iNOS and pro-inflammatory cytokines along with the parallel increase of Arg-1 and anti-inflammatory cytokines. Taken together, these data suggest that FAAH inhibition promotes cytoskeleton reorganization, regulates phagocytosis and cell migration processes, thus driving microglial polarization towards an anti-inflammatory phenotype. 
  • 591
  • 02 Aug 2021
Topic Review
Current Methodologies for Visualizing ATP in Living Cells
Measuring total ATP levels within cellular compartmental pools in real-time presents a newer and more innovative approach to qualitatively analyzing ATP. Although this method is not precisely quantitative, it can be helpful in determining changes in ATP concentrations in one region of a cell compared to another in a variety of disease states. The overall goal of these assays and imaging methodologies are to evaluate and visualize dynamic ATP trends, such as usage and depletion, between cells and their sub-compartments. However, semi-quantitative evaluation of the relative ATP signal is feasible. The currently developed technologies that utilize this approach to ATP quantification are mainly genetically encoded biosensors. In conjunction with a fluorescent or bioluminescent protein, most of these biosensors harness the folding capabilities of the ϵ subunit of the bacterial ATP synthase subunit. The bacterial ATP synthase protein comprises a β-barrel domain located at the N terminus and an α-helical domain with two α-helices located at the C terminus. Upon ATP binding, the two α-helices interact and refine their conformational structure of the ϵ subunit, leading to fluorescent/bioluminescent illumination, indicating that ATP is present. Overall, this subunit adopts two different conformations: open (ATP-free) or closed (ATP-bound). The uses and applicability of this technology are limitless. 
  • 590
  • 24 Jun 2022
Topic Review
Senescent Cells in Cutaneous Wound Healing
Cellular senescence has gained increasing attention in the field of aging research. Senescent cells have been implicated in biological aging processes, tumorigenesis, development, and wound repair amongst other processes and pathologies. Recent findings reveal that senescent cells can both promote and inhibit cutaneous wound healing processes. 
  • 590
  • 26 Dec 2022
Topic Review
Alpha-Thalassemia
Alpha-thalassemia (α-thalassemia, α-thalassaemia) is a form of thalassemia involving the genes HBA1 and HBA2. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood. Normal hemoglobin consists of two alpha chains and two beta chains; in alpha-thalassemia, there is a quantitative decrease in the amount of alpha chains, resulting in fewer normal hemoglobin molecules. Furthermore, alpha-thalassemia leads to the production of unstable beta globin molecules which cause increased red blood cell destruction. The degree of impairment is based on which clinical phenotype is present (how many genes are affected).
  • 589
  • 31 Oct 2022
Topic Review
Histone Genes in Drosophila
The evolution of the GC (guanine cytosine) content at the third codon position of the histone genes (H1, H2A, H2B, H3, H4, H2AvD, H3.3A, H3.3B, and H4r) in 12 or more Drosophila species is reviewed. For explaining the evolution of the GC content at the third codon position of the genes, a model assuming selection with a deleterious effect for adenine/thymine and a size effect is presented. The applicability of the model to whole-genome genes is also discussed. 
  • 589
  • 27 May 2021
Topic Review
Stem Cells and the Endometrium
Adult stem cells (ASCs) were long suspected to exist in the endometrium. Indeed, several types of endometrial ASCs were identified in rodents and humans through diverse isolation and characterization techniques. Putative stromal and epithelial stem cell niches were identified in murine models using label-retention techniques. In humans, functional methods (clonogenicity, long-term culture, and multi-lineage differentiation assays) and stem cell markers (CD146, SUSD2/W5C5, LGR5, NTPDase2, SSEA-1, or N-cadherin) facilitated the identification of three main types of endogenous endometrial ASCs: stromal, epithelial progenitor, and endothelial stem cells. Further, exogenous populations of stem cells derived from bone marrow may act as key effectors of the endometrial ASC niche.
  • 588
  • 29 Apr 2021
Topic Review
Type I Interferon
Together with type III IFNs, Type I Interferons (IFNs-I) represent the first line of immune defense against viral infections. In the case of RNA viruses, after recognition of viral products by pattern recognition receptors (PRRs), such as the main cytosolic receptors RNA helicases retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), the signal converges on the activation of the mitochondrial antiviral signaling protein (MAVS), that, in turns, activates the TANK-binding kinase 1 (TBK1), leading to the phosphorylation and activation of IFN-regulatory factors 3 and 7 (IRF3, IRF7) [6,7]. IRFs then translocate to the nucleus and induce the production of IFNs-I (IFNα, IFNβ, IFNε, IFNτ, IFNκ, IFNω, IFNδ and IFNζ).
  • 590
  • 07 Sep 2021
Topic Review
Intermediate Filaments in the Endothelial Cell
Vimentin, the main protein of endothelial intermediate filaments, is one of the most well-studied of these and belongs to type-III intermediate filaments, commonly found in cells of mesenchymal origin. Vimentin filaments are linked mechanically or by signaling molecules to microfilaments and microtubules by which coordinated cell polarisation and migration are carried out, as well as control over several endotheliocyte functions. Moreover, the soluble vimentin acts as an indicator of the state of the cardiovascular system, and the involvement of vimentin in the development and course of atherosclerosis has been demonstrated.
  • 588
  • 20 Apr 2022
Topic Review
Intestinal Cell Plasticity
Under constant barrage from chemical, pathogenic, and mechanical stresses, the intestinal epithelium is homeostatically replenished by a pool of Lgr5⁺ intestinal stem cells (ISCs), residing at the bottom of submucosal invaginations termed crypts. Decorated with the RSPO-receptor LGR5, which potentiates canonical Wnt/β-catenin signalling, these actively cycling cells can both self-renew and give rise to short-lived transit-amplifying cells. In turn, transit-amplifying cells undergo successive rounds of cell division and differentiation to generate the full gamut of terminally differentiated intestinal cell types tasked with performing pleiotropic absorptive, secretory, immune, and barrier functions. The self-renewal capabilities and multipotency of Lgr5⁺ ISCs are tightly controlled by instructive cues emanating from epithelial and stromal components of the ISC niche in the vicinity of the lower crypt.  The intestinal epithelium displays a remarkable ability to regenerate following demise of homeostatic Lgr5⁺ ISCs post injury. Plasticity—the ability of lineage-restricted cells to regain self-renewal capacity and multi-lineage differentiation potential in response to environmental cues—is pervasive among multiple intestinal cell populations. Reserve stem-like cells, lineage-committed progenitors, and/or fully differentiated cell types can all contribute to regeneration and repair through dedifferentiation and reversion to an Lgr5⁺ stem-like state. In line with the pervasive plasticity of the intestinal epithelium, accumulating evidence supports both “bottom-up” and “top-down” histogenesis of colorectal tumours whereby the cells-of-origin comprise either ISCs at the crypt base or differentiated cells at the crypt apex, respectively. 
  • 588
  • 30 Mar 2021
Topic Review
Protein Kinase CK2
Protein kinase CK2 (CK2) is a ubiquitous holoenzyme involved in a wide array of developmental processes. The involvement of CK2 in events such as neurogenesis, cardiogenesis, skeletogenesis, and spermatogenesis is essential for the viability of almost all organisms, and its role has been conserved throughout evolution.
  • 586
  • 02 Sep 2022
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