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Topic Review
Biography
Topic Review
Hyperprogressive Disease
Hyperprogressive disease (HPD) is an adverse outcome of immunotherapy consisting in an acceleration of tumor growth, often accompanied by prompt clinical deterioration.
501
27 May 2021
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.
501
22 Sep 2021
Topic Review
Application of Calcitriol in Breast Cancer
Calcitriol represents the most active VD metabolite and hormonal form, which modulates calcium homeostasis through actions on the kidney, bone, and intestinal tract. However, calcitriol is also known for its potent anticancer effects. In particular, calcitriol inhibits breast cancer cells proliferation and tumorigenesis.
501
03 Dec 2021
Topic Review
Efficient Mucosal Repair Limits Morbidity from Colic
Colic is a leading cause of death in horses, with the most fatal form being strangulating obstruction which directly damages the intestinal barrier. Following surgical intervention, it is imperative that the intestinal barrier rapidly repairs to prevent translocation of gut bacteria and their products and ensure survival of the patient. Age-related disparities in survival have been noted in many species, including horses, humans, and pigs, with younger patients suffering poorer clinical outcomes. Maintenance and repair of the intestinal barrier is regulated by a complex mucosal microenvironment, of which the ENS, and particularly a developing network of subepithelial enteric glial cells, may be of particular importance in neonates with colic. Postnatal development of an immature enteric glial cell network is thought to be driven by the microbial colonization of the gut and therefore modulated by diet-influenced changes in bacterial populations early in life.
501
13 Dec 2021
Topic Review
Doublecortin
Doublecortin (DCX) is a microtubule associated protein, essential for correct central nervous system development and lamination in the mammalian cortex. It has been demonstrated to be expressed in developing but not in mature neurons. The teleost visual system is an ideal model to study mechanisms of adult neurogenesis due to its continuous life-long growth. Immunohistochemical, in silico, and western blot analysis to detect the DCX protein in the visual system of teleost fish are described here.
501
23 Feb 2022
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.
500
14 May 2021
Topic Review
Exploiting DNA Replication Stress in Breast Cancer Treatment
Proliferating cells rely on DNA replication to ensure accurate genome duplication. Cancer cells, including breast cancer cells, exhibit elevated replication stress (RS) due to the uncontrolled oncogenic activation, loss of key tumor suppressors, and defects in the DNA repair machinery. This intrinsic vulnerability provides a great opportunity for therapeutic exploitation. An increasing number of drug candidates targeting RS in breast cancer are demonstrating promising efficacy in preclinical and early clinical trials.
500
08 Dec 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.
499
12 Jan 2023
Topic Review
Warburg Effect
Otto Warburg discovered that cancer cells use a fermentative rather than oxidative metabolism even though the former is more inefficient in terms of energy production per molecule of glucose. Cancer cells increase the use of this fermentative metabolism even in the presence of oxygen, and this process is called aerobic glycolysis or the Warburg effect.
499
14 Jun 2023
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.
498
22 Sep 2021
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