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Topic Review
Biography
Topic Review
Curaxins and G-Quadruplex DNA Oligomers
Curaxins and especially the second-generation derivative curaxin CBL0137 have important antitumor activities in multiple cancers such as glioblastoma, melanoma and others. Although most of the authors suggest that their mechanism of action comes from the activation of p53 and inactivation of NF-kB by targeting FACT, there is evidence supporting the involvement of DNA binding in their antitumor activity. In this work, the DNA binding properties of curaxin CBL0137 with model quadruplex DNA oligomers were studied by 1H NMR, CD, fluorescence and molecular modeling. We provided molecular details of the interaction of curaxin with two G-quadruplex structures, the single repeat of human telomere d(TTAGGGT)4 and the c-myc promoter Pu22 sequence.
765
17 Nov 2021
Topic Review
Cytoskeleton Reorganization in EndMT
EndMT-derived cells, known as the myofibroblasts or cancer-associated fibroblasts (CAFs), are characterized by the loss of cell–cell junctions, loss of endothelial markers, and gain in mesenchymal ones.
663
16 Nov 2021
Topic Review
Transthyretin: Osteoarticular and Cardiovascular Diseases
Transthyretin (TTR) is a tetrameric protein transporting hormones in the plasma and brain, which has many other activities that have not been fully acknowledged. TTR is a positive indicator of nutrition status and is negatively correlated with inflammation. TTR is a neuroprotective and oxidative-stress-suppressing factor.
474
16 Nov 2021
Topic Review
Quantitative Super-Resolution Imaging and GPCR Oligomerization Analysis
G-protein coupled receptors (GPCRs) are the largest family of cell surface receptors in eukaryotic cells. These seven-transmembrane receptors have influence in physiological events such as cell to cell communication, immune responses, nerve transmission and even hunger and sleep regulation. The role of GPCRs in diseases such as rheumatoid arthritis, heart disease, cancer, obesity, and neurodegenerative disorders accentuates the need to investigate this family of receptors further. More than a third of all drugs approved by the FDA target GPCRs but often such drugs have a variety of poorly understood mechanisms, as a recent example surrounding opioid receptor agonists illustrates.
446
15 Nov 2021
Topic Review
Aging and Bone Marrow
The aging of bone marrow (BM) remains a very imperative and alluring subject, with an ever-increasing interest among fellow scientists. A considerable amount of progress has been made in this field with the established ‘hallmarks of aging’ and continued efforts to investigate the age-related changes observed within the BM. Inflammaging is considered as a low-grade state of inflammation associated with aging, and whilst the possible mechanisms by which aging occurs are now largely understood, the processes leading to the underlying changes within aged BM remain elusive. The ability to identify these changes and detect such alterations at the genetic level are key to broadening the knowledgebase of aging BM. Next-generation sequencing (NGS) is an important molecular-level application presenting the ability to not only determine genomic base changes but provide transcriptional profiling (RNA-seq), as well as a high-throughput analysis of DNA–protein interactions (ChIP-seq). Utilising NGS to explore the genetic alterations occurring over the aging process within alterative cell types facilitates the comprehension of the molecular and cellular changes influencing the dynamics of aging BM.
564
15 Nov 2021
Topic Review
Myelin Basic Protein Interaction Landscape
Intrinsically disordered myelin basic protein (MBP) is one of the key autoantigens in autoimmune neurodegeneration and multiple sclerosis particularly. MBP is highly positively charged and lacks a distinct structure in solution, and therefore its intracellular partners are still mostly enigmatic. Here authors used combination of formaldehyde-induced cross-linking followed by immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the interaction network of MBP in mammalian cells and provide the list of potential MBP interacting proteins.
448
15 Nov 2021
Topic Review
Dietary Antioxidants in Age-Related Macular Degeneration and Glaucoma
Age-related macular degeneration (AMD) and glaucoma are ophthalmic neurodegenerative diseases responsible for irreversible vision loss in the world population. Only a few therapies can be used to slow down the progression of these diseases and there are no available treatment strategies for reversing the degeneration of the neural retina. In AMD, the pathological process causes the malfunction and damage of the retinal pigmented epithelium and photoreceptors in the macula. In glaucoma, damage of the retinal ganglion cells and their axons is observed and treatment strategies are limited to intraocular pressure lowering. Therefore, other prophylactic and/or therapeutic methods are needed. Oxidative stress is involved in the neurodegenerative process accompanying both AMD and glaucoma; therefore, the use of antioxidant agents would clearly be beneficial, which is supported by the decreased prevalence and progression of AMD in patients adherent to a diet naturally rich in antioxidants.
623
11 Nov 2021
Topic Review
PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior
Despite comprehensive therapy and extensive research, glioblastoma (GBM) still represents the most aggressive brain tumor in adults. Glioma stem cells (GSCs) are thought to play a major role in tumor progression and resistance of GBM cells to radiochemotherapy. The PIM1 kinase has become a focus in cancer research.
448
11 Nov 2021
Topic Review
Autonomy in Stem Cell-Derived Embryoids
The experimental production of complex structures resembling mammalian embryos (e.g., blastoids, gastruloids) from pluripotent stem cells in vitro has become a booming research field. Since some of these embryoid models appear to reach a degree of complexity that may come close to viability, a broad discussion has set in with the aim to arrive at a consensus on the ethical implications with regard to acceptability of the use of this technology with human cells. The present text focuses on developmental autonomy of embryoids which is an aspect of great ethical relevance and must receive increased attention during the preparation of new legal regulations, but which has not been included yet in the recently issued ISSCR Guidelines.
728
10 Nov 2021
Topic Review
Mutations in TSC Genes and Synaptic Transmission
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease featuring localized uncontrolled growth of tissues, known as hamartomas, in many organs, including the central nervous system (CNS). A large proportion of the cases are sporadic mutations (ca. two thirds). The disease results from a loss-of-function mutation in either the TSC1 or TSC2 gene, which encode for hamartin and tuberin proteins, respectively; two proteins that together form the Tsc1–Tsc2 complex. This complex, which is the converging center of several signaling pathways, has GTPase activity and can inhibit the activity of Ras homolog enriched in the brain (Rheb). The complex itself is modulated by phosphorylation via, for example, Akt or AMPK (Figure 1).
544
09 Nov 2021
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