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Topic Review
Biography
Topic Review
Glutamate-Glutamine Cycle
In biochemistry, the glutamate-glutamine cycle is a sequence of events by which an adequate supply of the neurotransmitter glutamate is maintained in the central nervous system. Neurons are unable to synthesize either the neurotransmitter glutamate or γ-aminobutyric acid (GABA) from glucose. Discoveries of glutamine and glutamate pools within intercellular compartments led to suggestions of the glutamate-glutamine cycle working between neurons and astrocytes. The glutamate/GABA-glutamine cycle is a metabolic pathway that describes the release of glutamate or GABA from neurons which are then taken up into astrocytes (star-shaped glial cells). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of glutamate or GABA.
458
27 Oct 2022
Topic Review
Stress Accelerates Tumor Progression via Sympathetic Nervous System
The sympathetic nervous system (SNS) originates in the ventral brainstem, where sympathetic premotor neurons are found. They are found predominantly in the rostral ventrolateral medulla (RVLM) and in the rostral ventromedial medulla (RVMM). These neurons project to the intermediolateral nucleus (IML, also known as the sympathetic preganglionic nucleus), which then projects to the dorsal root ganglia (DRG) for terminal output to peripheral organs which control heart rate, blood pressure, respiration, glycemia, vigilance and other physiological responses. When negative emotions are induced under chronic stress, the sympathetic nervous system is continuously activated and increases the release of catecholamines (such as epinephrine and norepinephrine). In a spontaneous colon tumor model, ablation of sympathetic premotor neurons in APCmin/+ mice reduces the number of polyps in the mouse intestine. Sympathetic denervation also leads to decreased tumorigenesis in a spontaneous prostate tumor mouse model. These results suggest that loss of SNS function may slow tumorigenesis.
458
01 Nov 2022
Topic Review
Microglia Heterogeneity and Function
Microglia are the resident immune cells of the central nervous system (CNS) that have distinct ontogeny and transcriptomic signatures than other tissue macrophages. Microglia play a pivotal role in the CNS homeostasis and diseases. Microglia express a battery of receptors for environmental cues and rapidly react to the changes in their microenvironment. This plasticity is attributed to the ability of microglia to adapt a context-specific phenotype.
457
27 Apr 2021
Topic Review
Mesenchymal Stem Cell
Mesenchymal stem cells have generated a great deal of interest due to their potential use in regenerative medicine and tissue engineering. Examples illustrating their therapeutic value across various in vivo models are demonstrated in the literature. However, some clinical trials have not proved their therapeutic efficacy, showing that translation into clinical practice is considerably more difficult and discrepancies in clinical protocols can be a source of failure. Among the critical factors which play an important role in MSCs’ therapeutic efficiency are the method of preservation of the stem cell viability and various characteristics during their storage and transportation from the GMP production facility to the patient’s bedside. The cell storage medium should be considered a key factor stabilizing the environment and greatly influencing cell viability and potency and therefore the effectiveness of advanced therapy medicinal product (ATMP) based on MSCs.
457
14 May 2021
Topic Review
Chemokine uptake in Endothelial Cells
The chemokines CCL5 and CXCL4 are deposited by platelets onto endothelial cells, inducing monocyte arrest. Here, the fate of CCL5 and CXCL4 after endothelial deposition was investigated. Human umbilical vein endothelial cells (HUVECs) and EA.hy926 cells were incubated with CCL5 or CXCL4 for up to 120 min, and chemokine uptake was analyzed by microscopy and by ELISA. Intracellular calcium signaling was visualized upon chemokine treatment, and monocyte arrest was evaluated under laminar flow. Whereas CXCL4 remained partly on the cell surface, all of the CCL5 was internalized into endothelial cells. Endocytosis of CCL5 and CXCL4 was shown as a rapid and active process that primarily depended on dynamin, clathrin, and G protein-coupled receptors (GPCRs), but not on surface proteoglycans. Intracellular calcium signals were increased after chemokine treatment. Confocal microscopy and ELISA measurements in cell organelle fractions indicated that both chemokines accumulated in the nucleus. Internalization did not affect leukocyte arrest, as pretreatment of chemokines and subsequent washing did not alter monocyte adhesion to endothelial cells. Endothelial cells rapidly and actively internalize CCL5 and CXCL4 by clathrin and dynamin-dependent endocytosis, where the chemokines appear to be directed to the nucleus. These findings expand our knowledge of how chemokines attract leukocytes to sites of inflammation.
457
22 Sep 2021
Topic Review
VAV Proteins
The VAV GEF family has been traditionally linked to protumorigenic actions in cancer. This idea was reinforced by the use of both cancer cell lines and mouse models demonstrating the proactive role of VAV proteins in the development of different types of tumors, such as skin and breast cancer. However, given the presence of structural domains that facilitate the interaction with a large number of protein partners and the particular features of some of the VAV-dependent pathways, it is conceivable that VAV proteins might antagonize cell transformation in certain in vivo contexts.
456
27 Oct 2021
Topic Review
FAK Inhibition and Corneal Fibroblast Differentiation in vitro
Fibrosis is often known as a response of a tissue to injury, and since the three transforming growth factor-beta (TGF-β) isoforms (TGF-β1, -β2, and -β3) are the main regulators of cell migration, differentiation, proliferation, and gene expression, they were implicated in both reparative and fibrotic responses. All three TGF-β isoforms are homologues, sharing an extensive similarity in their amino acid sequences (80%), which may result in overlapping functions (i.e., SMAD-dependent signaling, modulating inflammatory responses); however, subtle differences in the sequences exist, thus potentially eliciting opposing effects. For example, several studies showed that TGF-β1 and -β2 are factors that drive the formation of fibrosis in corneal scarring models [8,9,10], whereas TGF-β3 was reported to downregulate fibrosis and promote scarless wound healing (healing without fibrosis).
456
29 Mar 2022
Topic Review
Rieske Iron-Sulfur Protein in COPD and Pulmonary Hypertension
Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death worldwide. The development of pulmonary hypertension (PH) accounts for the high mortality rate in COPD patients. Recent studies from the researchers' laboratory and others have highlighted the important role of reactive oxygen species (ROS) signaling in the development of COPD and associated PH. ROS are primarily generated in mitochondrial complex III in pulmonary artery smooth muscle cells (PASMCs). Rieske iron-sulfur protein (RISP), a catalytic subunit of mitochondrial complex III, is the major player in the generation of ROS. RISP plays a critical role in pulmonary vasoconstriction, remodeling, and hypertension.
456
17 Nov 2022
Topic Review
Chromogranin A -Derived Peptides as Inflammatory Modulator Molecules
Chromogranin A (CgA) is a glyco-phosphoprotein discovered for the first time in the adrenal medulla but also produced in several cells. CgA can generate different derived antimicrobial peptides (AMPs) influencing numerous physiological processes. CgA-derived peptides modulate inflammation and represent an example of endogenous Multifunctional AMPs (MF-AMPs).
456
21 Oct 2022
Topic Review
ORP5 and ORP8
Oxysterol binding related proteins 5 and 8 (ORP5 and ORP8) are two close homologs of the larger oxysterol binding protein (OSBP) family of sterol sensors and lipid transfer proteins (LTP). Early studies indicated these transmembrane proteins, anchored to the endoplasmic reticulum (ER), bound and sensed cholesterol and oxysterols. They were identified as important for diverse cellular functions including sterol homeostasis, vesicular trafficking, proliferation and migration. In addition, they were implicated in lipid-related diseases such as atherosclerosis and diabetes, but also cancer, although their mechanisms of action remained poorly understood. Then, alongside the increasing recognition that membrane contact sites (MCS) serve as hubs for non-vesicular lipid transfer, added to their structural similarity to other LTPs, came discoveries showing that ORP5 and 8 were in fact phospholipid transfer proteins that rather sense and exchange phosphatidylserine (PS) for phosphoinositides, including phosphatidylinositol-4-phosphate (PI(4)P) and potentially phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2). Evidence now points to their action at MCS between the ER and various organelles including the plasma membrane, lysosomes, mitochondria, and lipid droplets. Dissecting exactly how this unexpected phospholipid transfer function connects with sterol regulation in health or disease remains a challenge for future studies.
455
15 Jul 2021
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