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Topic Review
B-Cell Receptor Signaling Regulation and Aggressive B-Cell Lymphomas
The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B-cell non-Hodgkin lymphomas (B-NHLs). The emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton’s tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma such as diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. 
  • 532
  • 03 Mar 2022
Topic Review
CIDE Proteins in Human Health
Cell death-Inducing DNA Fragmentation Factor Alpha (DFFA)-like Effector (CIDE) proteins have emerged as lipid droplet-associated proteins that regulate fat metabolism. There are three members in the CIDE protein family—CIDEA, CIDEB, and CIDEC (also known as fat-specific protein 27 (FSP27)). CIDEA and FSP27 are primarily expressed in adipose tissue, while CIDEB is expressed in the liver. Originally, based upon their homology with DNA fragmentation factors, these proteins were identified as apoptotic proteins. However, recent studies have changed the perception of these proteins, redefining them as regulators of lipid droplet dynamics and fat metabolism, which contribute to a healthy metabolic phenotype in humans. Despite various studies in humans and gene-targeting studies in mice, the physiological roles of CIDE proteins remains elusive.
  • 532
  • 07 Jun 2022
Topic Review
Membrane Lipids in Light-Activation of Drosophila TRP Channels
Transient Receptor Potential (TRP) channels constitute a large superfamily of polymodal channel proteins with diverse roles in many physiological and sensory systems that function both as ionotropic and metabotropic receptors. From the early days of TRP channel discovery, membrane lipids were suggested to play a fundamental role in channel activation and regulation. A prominent example is the Drosophila TRP and TRP-like (TRPL) channels, which are predominantly expressed in the visual system of Drosophila. Light activation of the TRP and TRPL channels, the founding members of the TRP channel superfamily, requires activation of phospholipase Cβ (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into Diacylglycerol (DAG) and Inositol 1, 4,5-trisphosphate (IP3).
  • 532
  • 19 Apr 2022
Topic Review
Platelet Concentrates
Platelet concentrates (PCs) typically refer to a group of materials produced from autologous blood designed to improve tissue regeneration.
  • 531
  • 19 Feb 2021
Topic Review
ZEB1 in Cornea
ZEB1 is an important transcription factor for epithelial to mesenchymal transition (EMT) and in the regulation of cell differentiation and transformation. In the cornea, ZEB1 presents in all three layers: the epithelium, the stroma and the endothelium. Mutations of ZEB1 have been linked to multiple corneal genetic defects, particularly to the corneal dystrophies including keratoconus (KD), Fuchs endothelial corneal dystrophy (FECD), and posterior polymorphous corneal dystrophy (PPCD).
  • 531
  • 22 Apr 2021
Topic Review
Induced Nephron Progenitor-like Cells from Human Urine-Derived Cells
Chronic kidney disease (CKD) has emerged as a major public health concern due to its prevalence in 7–12% of the population worldwide, progression to irreversible end-stage renal disease (ESRD), impaired quality of life, associations with high social and financial costs, and high rates of associated morbidity and mortality (an 82% increase in CKD epidemic over the past two decades). The current treatment options for kidney failure involve lifelong dialysis and whole kidney transplantation. Although kidney transplantation undoubtedly offers a better quality of life and life expectancy than dialytic treatment, it is limited by the scarcity of available organs and the huge gap between supply and demand. Furthermore, considering that the average life expectancy of dialysis patients is barely a decade, alternative strategies for preventing or delaying the progression to ESRD are urgently needed. In this context, regenerative medicine strategies employing nephron progenitor cells (NPCs) are a viable approach that is worthy of substantial consideration as a promising cell source for kidney diseases. However, the generation of induced nephron progenitor-like cells (iNPCs) from human somatic cells remains a major challenge.
  • 531
  • 24 Dec 2021
Topic Review
CRISPR Screen
Genome-wide CRISPR/Cas9 screen provides a robust and unbiased means for interrogating such genes, and a series of landmark reports since its introduction in 2014 have demonstrated that the technology yields high-quality functional hits. This technology, in combination with other orthogonal methods for studying protein function on a systems scale, can provide valuable functional insights that would take years to establish using conventional methods.
  • 530
  • 01 Dec 2021
Topic Review
Core PCP Proteins in Coordinating Cilia Orientation
As exemplified by the unidirectionally beating cilia of multi-ciliated cells, various epithelial cells polarize not only along the apical-basal axis (inside–outside axis) of epithelial tissues, but also on the plane of epithelial tissues. The latter cell polarity, which is perpendicular to the apical–basal axis, is referred to as planar cell polarity (PCP). Pioneering research using the wings of Drosophila melanogaster identified a group of proteins, core PCP proteins, that orchestrate the establishment of PCP.
  • 530
  • 21 Nov 2022
Topic Review
SUMOylation
SUMOylation is a dynamic and essential Post-Translation Modification (PTM) consisting on the conjugation of Small Ubiquitin-like Modifiers (SUMOs) to an acceptor lysine of a substrate protein. SUMOylation predominantly regulates nuclear processes and its dysregulation is associated to diseases including cancer. SUMOs share a similar three-dimensional structure with other Ubiquitin-Like Modifiers (UBLs). However, SUMOs differ due to their flexible N-terminus, which also contains the site for SUMO chain formation. All eukaryotes express at least one SUMO paralogue. Five SUMO family members have been identified in humans (SUMO1, SUMO2, SUMO3, SUMO4, and SUMO5. However, SUMO1, SUMO2, and SUMO3 are the main family members where they are commonly classified as SUMO1 and SUMO2/3 because of the high similarity between mature SUMO2 and SUMO3. All SUMO paralogues are similar in structure but differ in expression levels. SUMO2 is the most abundant family member in mammalian cells. Studies in mice show that the knockout of SUMO2 is embryonic lethal, while SUMO1 and SUMO3 knockout mice were associated to mild phenotypes, possibly because SUMO2 might compensate the loss of either SUMO1 or SUMO3. Similarly to ubiquitination, SUMO is conjugated in a in a 3-step enzymatic cascade that involves a dimeric E1 activating enzyme (SAE1 and SAE2), an E2 conjugating enzyme (Ubc9), and several SUMO E3 enzymes.
  • 529
  • 28 Mar 2022
Topic Review
Therapeutic Potential of MSC-EVs in Neurodegenerative Disorders
The application of mesenchymal stem cells (MSCs) represents a new promising approach for treating neurodegenerative diseases. Growing evidence suggests that the therapeutic effects of MSCs are due to the secretion of neurotrophic molecules through extracellular vesicles. The extracellular vesicles produced by MSCs (MSC-EVs) have valuable innate properties deriving from parental cells and could be exploited as cell-free treatments for many neurological diseases.
  • 529
  • 23 Feb 2023
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