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Topic Review
Agonists for Peroxisome Proliferator-Activated Receptors
Nuclear receptors (NRs) are ligand-dependent transcription factors that modulate diverse aspects of development, reproduction, and energy homeostasis. This receptor superfamily includes receptors for vitamin D, steroid hormones, thyroid hormones and retinoids, as well as a large number of orphan receptors. NRs are composed of six functionally distinct regions (termed A to F). The N-terminal AB region is highly variable and contains a constitutionally active transactivation function-1 (AF-1) motif. The central C region (a DNA-binding region) is highly conserved among NRs and contains two zinc finger motifs that make contact with specific nucleotide sequences, termed hormone response elements. The C-terminal D, E and F regions are required for ligand binding and receptor dimerization. In most NRs, these regions also contain a second highly conserved transcriptional activation function-2 (AF-2) motif, which is important for ligand-dependent transcription.
  • 427
  • 07 Sep 2021
Topic Review
Nodal Proteins
Nodal proteins show a different affinity to TGF-β receptors; it was demonstrated that the presence of binding proteins that act as partners enhances the signal cascade, improving the interactions between Nodal and its receptors. It was established that a fundamental obligatory co-receptor for the TGF-β family member Nodal is the cell surface glycosylphosphatidylinositol (GPI)-linked glycoprotein Cripto-1 (CR-1). Co-immunoprecipitation experiments show the interaction between Nodal and CR-1, supporting the idea that CR-1 acts as an obliged coreceptor for Nodal that potentiates its signal cascade.
  • 743
  • 07 Sep 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).
  • 564
  • 07 Sep 2021
Topic Review
LncRNAs in Age-Related Macular Degeneration
lncRNAs are a novel class of functional RNA; the landscape of their mutations and variations is small as compared with other ncRNAs, not to mention mRNAs. However, the variability of lncRNA-encoding genes in the pathogenesis of human diseases, especially in cancer, is emerging (reviewed in the work of), but we have not found any association of lncRNA we described in this review with AMD. On the other hand, AMD is reported to associate with mutations in hundreds of genes, often in the form of polymorphisms, which should be considered in experimental studies and projection of therapeutic interventions (reviewed in the work of).
  • 313
  • 06 Sep 2021
Topic Review
Aquaporin Inhibitors
Aquaporins (AQPs) are water channel proteins that are essential to life, being expressed in all kingdoms. In humans, there are 13 AQPs, at least one of which is found in every organ system. The structural biology of the AQP family is well-established and many functions for AQPs have been reported in health and disease. AQP expression is linked to numerous pathologies including tumor metastasis, fluid dysregulation, and traumatic injury. The targeted modulation of AQPs therefore presents an opportunity to develop novel treatments for diverse conditions. Various techniques such as video microscopy, light scattering and fluorescence quenching have been used to test putative AQP inhibitors in both AQP-expressing mammalian cells and heterologous expression systems. The inherent variability within these methods has caused discrepancy and many molecules that are inhibitory in one experimental system (such as tetraethylammonium, acetazolamide, and anti-epileptic drugs) have no activity in others. Some heavy metal ions (that would not be suitable for therapeutic use) and the compound, TGN-020, have been shown to inhibit some AQPs. Clinical trials for neuromyelitis optica treatments using anti-AQP4 IgG are in progress. However, these antibodies have no effect on water transport. More research to standardize high-throughput assays is required to identify AQP modulators for which there is an urgent and unmet clinical need.
  • 4.0K
  • 06 Sep 2021
Topic Review
Comparison of Histone H3K4me3
Histones are alkaline proteins that package DNA into nucleosomes. H3K4me3 is highly enriched in gene promoter regions. A gain in H3K4me3 enrichment is associated with active gene transcription, open chromatin, and loss of DNA methylation. H3K4me3 has been adopted as a marker to identify transcriptionally active genes.
  • 529
  • 03 Sep 2021
Topic Review
Neural Stem and Progenitor Cells
Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration.
  • 753
  • 03 Sep 2021
Topic Review
Pluripotency
Following fertilization, in the mammalian embryo, a series of programmed cell divisions occur whereby the arising cells progressively acquire their own cellular and molecular identity, and totipotency narrows until when pluripotency is achieved. The path towards pluripotency involves transcriptome modulation, remodeling of the chromatin epigenetic landscape to which external modulators contribute. Both human and mouse embryos are a source of different types of pluripotent stem cells whose characteristics can be captured and maintained in vitro. 
  • 900
  • 03 Sep 2021
Topic Review
Nanoparticles to Treat Macrophages
Nanoparticles are nanomaterials with three external nanoscale dimensions and an average size ranging from 1 to 1000 nm. Nanoparticles have gained notoriety in technological advances due to their tunable physical, chemical, and biological characteristics. However, the administration of functionalized nanoparticles to living beings is still challenging due to the rapid detection and blood and tissue clearance by the mononuclear phagocytic system. The major exponent of this system is the macrophage. Regardless the nanomaterial composition, macrophages can detect and incorporate foreign bodies by phagocytosis. Therefore, the simplest explanation is that any injected nanoparticle will be probably taken up by macrophages. This explains, in part, the natural accumulation of most nanoparticles in the spleen, lymph nodes, and liver (the main organs of the mononuclear phagocytic system). For this reason, recent investigations are devoted to design nanoparticles for specific macrophage targeting in diseased tissues. The aim of this review is to describe current strategies for the design of nanoparticles to target macrophages and to modulate their immunological function involved in different diseases with special emphasis on chronic inflammation, tissue regeneration, and cancer. 
  • 404
  • 02 Sep 2021
Topic Review
Insulin-Like Growth Factor System
Aberrant bioactivity of the insulin-like growth factor (IGF) system results in the development and progression of several pathologic conditions including cancer. Preclinical studies have shown promising anti-cancer therapeutic potentials for anti-IGF targeted therapies. However, a clear but limited clinical benefit was observed only in a minority of patients with sarcomas. The molecular complexity of the IGF system, which comprises multiple regulators and interactions with other cancer-related pathways, poses a major limitation in the use of anti-IGF agents and supports the need of combinatorial therapeutic strategies to better tackle this axis. 
  • 397
  • 02 Sep 2021
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