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Topic Review
Therapeutic Strategies for Leukemic Stem Cells
Notoriously known for their capacity to reconstitute hematological malignancies in vivo, leukemic stem cells (LSCs) represent key drivers of therapeutic resistance and disease relapse, posing as a major medical dilemma. Despite having low abundance in the bulk leukemic population, LSCs have developed unique molecular dependencies and intricate signaling networks to enable self-renewal, quiescence, and drug resistance. The abundance of molecular and phenotypical aberrations associated with LSCs offers a wealth of promising therapeutic targets. Therapeutic designs have focused on drugging surface biomarkers selectively overexpressed on LSCs, antagonizing the protective bone marrow (BM) microenvironment niche to dismantle LSC dormancy, blocking signal transduction to re-sensitize resistant LSCs to available chemotherapeutics, and even expediting the drug supply pipeline through drug repurposing. Evidently, growing insight into the biological properties and prognostic values of LSCs have prompted the implementation of many clinical trials and have laid critical groundwork for the development of more effective, personalized, scalable, and less-toxic therapeutic strategies.
  • 468
  • 08 Oct 2022
Topic Review
Methionine and Stemness
Stem cells are a population of undifferentiated cells with self-renewal and differentiation capacities. Normal and cancer stem cells share similar characteristics in relation to their stemness properties. One-carbon metabolism (OCM), a network of interconnected reactions, plays an important role in this dependence through its role in the endogenous synthesis of methionine and S-adenosylmethionine (SAM), the universal donor of methyl groups in eukaryotic cells. OCM genes are differentially expressed in stem cells, compared to their differentiated counterparts. Furthermore, cultivating stem cells in methionine-restricted conditions hinders their stemness capacities through decreased SAM levels with a subsequent decrease in histone methylation, notably H3K4me3, with a decrease in stem cell markers. Stem cells’ reliance on methionine is linked to several mechanisms, including high methionine flux or low endogenous methionine biosynthesis.
  • 468
  • 12 Jan 2023
Topic Review
CfDNA, Sport Adaptation Predictor
Changes of circulating free plasma DNA (cfDNA) are associated with different types of tissue injury, including those induced by intensive aerobic and anaerobic exercises. Observed changes are dependent from induced inflammation, and thus it may be a potential marker for athletic overtraining. 
  • 467
  • 26 Aug 2021
Topic Review
Sphingolipid Homeostasis
Sphingolipids are ubiquitous components of cellular membranes that exert various functions depending on their structural maturation and subcellular localization. Structurally simple sphingolipid precursors, such as ceramides, act as intracellular signaling molecules in many processes, including apoptosis, whereas mature and complex forms of sphingolipids are important structural components of the plasma membrane. Supplying complex sphingolipids to the plasma membrane while simultaneously preventing the accumulation of pro-apoptotic metabolites is essential for cell survival and depends on mechanisms that tightly control sphingolipid synthesis, breakdown, transport, and storage. Sphingolipid homeostasis describes the state of the cell in which the intracellular concentration and distribution of sphingolipids supports survival. 
  • 467
  • 22 Dec 2021
Topic Review
The “Prion-like” Nature of Tau and Its Strains
Tauopathies are a group of neurodegenerative diseases characterized by the hyperphosphorylation and deposition of tau proteins in the brain. In Alzheimer’s disease, and other related tauopathies, the pattern of tau deposition follows a stereotypical progression between anatomically connected brain regions. Increasing evidence suggests that tau behaves in a “prion-like” manner, and that seeding and spreading of pathological tau drive progressive neurodegeneration.
  • 467
  • 11 Oct 2022
Topic Review
Sphingolipids in Viral Infections
Sphingolipids (SLs) are highly abundant components of cellular membranes and as such, are essentially involved in their biophysical and signaling properties. A complex metabolic network consisting of enzymes catalyzing their synthesis, modification (phosphorylation, glycosylation) and breakdown regulates accumulation of sphingolipid species and thereby the sphingolipid pool at rheostat conditions, and this can undergo substantial changes in response to metabolic and external challenges. This has been excellently reviewedand will therefore just be briefly re-iterated below.
  • 466
  • 22 Sep 2021
Topic Review
Ultrasound-Mediated Drug Delivery and Gene Therapy
Ultrasound (US) is a nearly innocuous and widely available imaging technique with a well-established role in various diagnostic applications. Diagnostic US techniques uses high frequency ultrasound waves to view real-time tissue and organs inside the human body. The use of US as a drug delivery facilitator was first described in the mid 90s, using the physical transient increased cell membrane permeability from sonoporation. Subsequent research reported the enhanced biophysical effects of ultrasound by incorporation of MBs.
  • 466
  • 05 Nov 2021
Topic Review
Extracellular Vesicles for Cancer Gene Therapy
Extracellular vesicles (EVs) are nanoscale vesicles secreted by most types of cells as natural vehicles to transfer molecular information between cells. Due to their low toxicity and high biocompatibility, EVs have attracted increasing attention as drug delivery systems. Researchers summarize the techniques and methods to increase EV yield, enhance nucleic acid loading efficiency, extend circulation time, and improve targeted delivery. 
  • 466
  • 03 Nov 2022
Topic Review
COVID-19: the Immunological Challenges
Although COVID-19 pneumonia is a novel disease that is different from other types of ARDS, severe COVID-19-associated ARDS shares typical ARDS lung pathology such as diffuse alveolar damage and hyaline membrane formation. As Prasanna et al. summarized, the general rationale for low-dose radiation treatment of COVID-19 is its inhibition of the cytokine storm, which promotes pulmonary dysfunction and ultimately ARDS. Inflammation is a dynamic and progressive process that is tightly associated with redox-modulated reactions. When recruited to sites of inflammation, macrophages and neutrophils generate reactive species, including reactive oxygen and nitrogen species (ROS and RNS). With multiple pro-inflammatory cytokines and chemokines being secreted, the latter together with elevated levels of ROS and RNS deteriorate redox homeostasis, and further worsen the disease. During the past two decades, research has revealed that low-dose radiation-mediated homeostasis is associated with enhanced cellular detoxification of ROS by a major antioxidant enzyme (manganese superoxide dismutase, MnSOD) within the mitochondria. This adaptive protection of mitochondrial metabolic functions is thought to provide experimental and theoretical support for using low-dose radiation to limit virus replication. Other antioxidants, including glutathione, were also shown to be increased following exposure to low doses of sparsely ionizing radiation such as X and γ rays. Schaue et al. suggested that it might be difficult and challenging for patients with complicated conditions and advanced age to rebalance redox levels, and low-dose radiation treatment might be of clinical value with its broad suppression of various inflammatory, pro-oxidant pathways at multiple levels.
  • 467
  • 29 Sep 2021
Topic Review
Fibroblast Growth Factor 23
FGF23 is a bone-derived hormone that is essential for regulating vitamin D and phosphate homeostasis. 
  • 465
  • 29 Mar 2022
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