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Topic Review
Three-Dimensional Cell Cultures
Cell cultures are very important for testing materials and drugs, and in the examination of cell biology and special cell mechanisms. The most popular models of cell culture are two-dimensional (2D) as monolayers, but this does not mimic the natural cell environment. Cells are mostly deprived of cell–cell and cell–extracellular matrix interactions. A much better in vitro model is three-dimensional (3D) culture. Because many cell lines have the ability to self-assemble, one 3D culturing method is to produce spheroids. There are several systems for culturing cells in spheroids, e.g., hanging drop, scaffolds and hydrogels, and these cultures have their applications in drug and nanoparticles testing, and disease modeling.
  • 653
  • 27 Oct 2020
Topic Review
Natural Killer Cells
When facing an acute viral infection, our immune systems need to function with finite precision to enable the elimination of the pathogen, whilst protecting our bodies from immune-related damage. In many instances however this ‘perfect balance’ is not achieved, factors such as ageing, cancer, autoimmunity and cardiovascular disease all skew the immune response which is then further distorted by viral infection. SARS-CoV-2 infection skews the immune response towards an overwhelmingly inflammatory phenotype. Restoration of NK cell effector functions has the potential to correct the delicate immune balance required to effectively overcome SARS-CoV-2 infection.
  • 1.7K
  • 27 Oct 2020
Topic Review
Bacterial Virulence Factors
There are several levels to influence the expression of eukaryotic genes. A first level of interference is changing of the DNA’s structure on the chromatin level. Epigenetic modulation enables remodelling of the chromatin to transfer heterochromatin into euchromatin allowing transcription or vice versa. In addition, the affinity of promotors and other regulatory DNA sequences for RNA polymerases and transcription factors (TFs) can be influenced by cytosine or adenine methylation. Only a minor portion (fewer than 2%) of genes is transcribed into mRNAs, instead the majority is transferred into so called non-coding RNAs (ncRNAs). Certain long ncRNAs (lncRNAs) are also involved in epigenetic regulations. Epigenetic mechanisms are used for manipulation of gene expression in the course of several cellular processes. Here, we give an overview on the epigenetic control of gene expression by bacterial virulence factors during host cell infection.
  • 948
  • 27 Oct 2020
Topic Review
MiR-615
miR-615, a miRNA highly conserved across eutherian mammals. It is involved not only during embryogenesis in the regulation of growth and development, for instance during osteogenesis and angiogenesis, but also in the regulation of cell growth and the proliferation and migration of cells, acting as a tumor suppressor or tumor promoter. It, therefore, serves as a biomarker for several types of cancer and recently has also been found to be involved in reparative processes and neural repair.
  • 695
  • 27 Oct 2020
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.
  • 838
  • 27 Oct 2020
Topic Review
Adenosine in inflammation and neoplasia
Adenosine is a purine nucleoside, resulting from the degradation of adenosine triphosphate (ATP). Under adverse conditions, including hypoxia, ischemia, inflammation, or cancer, the extracellular levels of adenosine increase significantly. Once released, adenosine activates cellular signaling pathways through the engagement of the four known G-protein-coupled receptors, adenosine A1 receptor subtype (A1), A2A, A2B, and A3. These receptors, expressed virtually on all immune cells, mitigate all aspects of immune/inflammatory responses. These immunosuppressive effects contribute to blunt the exuberant inflammatory responses, shielding cells, and tissues from an excessive immune response and immune-mediated damage.
  • 1.2K
  • 27 Oct 2020
Topic Review
Primary Biliary Cholangitis
Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune liver disease characterized by inflammation and damage of small bile ducts that frequently progress to liver cirrhosis and predominantly affects females. The key moment in the pathophysiology of the disease is loss of tolerance to PDC-E2, pyruvate subunit of the complex of dehydrogenase enzyme, located in the mitochondrial membrane. Combined genetic, epigenetic and environmental factors trigger the initial damage of the biliary epithelium in PBC, followed by the multilineage immune/inflammatory response to damaged cholangiocytes resulting in development of chronic biliary inflammatory disease.
  • 534
  • 27 Oct 2020
Topic Review
High Mobility Group Box 1
The High Mobility Group Box 1 (HMGB1) is the most abundant nuclear nonhistone protein that is involved in transcription regulation. In addition, HMGB1 has previously been found as an extracellularly acting protein enhancing neurite outgrowth in cultured neurons. Although HMGB1 is widely expressed in the developing central nervous system of vertebrates and invertebrates, its function in the developing mouse brain is poorly understood. Here, we have analyzed developmental defects of the HMGB1 null mouse forebrain, and further examined our findings in ex vivo brain cell cultures. We find that HMGB1 is required for the proliferation and differentiation of neuronal stem cells/progenitor cells. Enhanced apoptosis is also found in the neuronal cells lacking HMGB1. Moreover, HMGB1 depletion disrupts Wnt/β-catenin signaling and the expression of transcription factors in the developing cortex, including Foxg1, Tbr2, Emx2, and Lhx6. Finally, HMGB1 null mice display aberrant expression of CXCL12/CXCR4 and reduced RAGE signaling. In conclusion, HMGB1 plays a critical role in mammalian neurogenesis and brain development.
  • 700
  • 27 Oct 2020
Topic Review
Actin Cytoskeleton in Podocytes
Proteinuria is one of the hallmarks of kidney disease. Serum proteins such as albumin are prevented from being filtered into the urine by the glomerular filtration barrier of which podocytes are a key part. Podocyte structure and function are dependent on maintenance of the actin cytoskeleton in podocyte foot processes. Foot processes contain two structural and signaling hubs: the slit diaphragm and focal adhesions, both of which maintain foot process integrity and relay signals to and from the podocyte exterior in response to hemodynamic changes. The entry below describes the key components of foot process actin cytoskeleton structure and regulation. 
  • 1.0K
  • 27 Oct 2020
Topic Review
Caloric Restriction
Caloric restriction (CR) is a traditional but scientifically verified approach to promoting health and increasing lifespan. CR exerts its effects through multiple molecular pathways that trigger major metabolic adaptations. It influences key nutrient and energy-sensing pathways including mammalian target of rapamycin, Sirtuin 1, AMP-activated protein kinase, and insulin signaling, ultimately resulting in reductions in basic metabolic rate, inflammation, and oxidative stress, as well as increased autophagy and mitochondrial efficiency.
  • 693
  • 27 Oct 2020
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