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Topic Review
Cancer Spheroids and Organoids
Spheroids and organoids are important novel players in medical and life science research. They are gradually replacing two-dimensional (2D) cell cultures. Indeed, three-dimensional (3D) cultures are closer to the in vivo reality and open promising perspectives for academic research, drug screening, and personalized medicine. A large variety of cells and tissues, including tumor cells, can be the starting material for the generation of 3D cultures, including primary tissues, stem cells, or cell lines.
  • 1.1K
  • 18 Apr 2023
Topic Review
Neutrophil Cell Death
Traditionally, neutrophils were seen as terminally differentiated cells destined to commit suicide on their one-way mission from bone marrow to the tissue. Neutrophils are an essential component of the innate immune response, but they are also a major contributor to inflammation. Neutrophil homeostasis is tightly regulated through balance between granulopoiesis, bone marrow storage and release, intravascular margination, and clearance of dying cells.
  • 1.1K
  • 22 Feb 2022
Topic Review
Therapeutic Stem Cell Banks
Stem cells are currently being used in many clinical trials for regenerative purposes. These are promising results for stem cells in the treatment of several diseases, including cancer. Nevertheless, there are still many variables which should be addressed before the application of stem cells for cancer treatment. One approach should be to establish well-characterized therapeutic stem cell banks to minimize the variation in results from different clinical trials and facilitate their effective use in basic and translational research. 
  • 1.1K
  • 27 Oct 2020
Topic Review
N-Terminal Methionine Excision
In the cytosol of human cells, when a newly synthesized polypeptide emerges from the ribosomes, its fate can be determined by the enzymes that modify its N-terminal α-amino acid residue (Nα). These N-terminal modifications include excision of the initiator methionine (iMet), Nα-myristoylation, Nα-acetylation, Nα-methylation, and other less common modification events. Methionine aminopeptidases (MetAPs) are responsible for N-terminal iMet excision (NME).
  • 1.1K
  • 14 Aug 2023
Topic Review
Impact of C99 on Alzheimer’s Disease
Amyloid beta (Aβ) is produced from a type-I transmembrane protein, amyloid beta precursor protein (APP). One of the APP metabolites, the 99-amino acids C-terminal fragment (C99, also called βCTF), is a direct precursor of Aβ and accumulates in the Alzheimer’s disease (AD) patient’s brain to demonstrate toxicity independent of Aβ. Conventional drug discovery strategies have focused on Aβ toxicity on the “outside” of the neuron, but C99 accumulation might explain the toxicity on the “inside” of the neuron, which was overlooked in the hypothesis. Furthermore, the common region of C99 and Aβ is a promising target for multifunctional AD drugs.
  • 1.1K
  • 21 Feb 2023
Topic Review
Mesenchymal Cells for RP Therapy
Retinitis pigmentosa (RP) is a complex inherited retinal dystrophy currently lacking effective therapies: this represents one of the greatest challenges in the field of ophthalmological research. Stem cells, especially mesenchymal cells represents a feasible therapeutic option in RP, limitating both oxidative stress and apoptotic processes triggered by the disease and promoting cell survival. 
  • 1.1K
  • 26 Oct 2020
Topic Review
Stem Cells and the Endometrium
Adult stem cells (ASCs) were long suspected to exist in the endometrium. Indeed, several types of endometrial ASCs were identified in rodents and humans through diverse isolation and characterization techniques. Putative stromal and epithelial stem cell niches were identified in murine models using label-retention techniques. In humans, functional methods (clonogenicity, long-term culture, and multi-lineage differentiation assays) and stem cell markers (CD146, SUSD2/W5C5, LGR5, NTPDase2, SSEA-1, or N-cadherin) facilitated the identification of three main types of endogenous endometrial ASCs: stromal, epithelial progenitor, and endothelial stem cells. Further, exogenous populations of stem cells derived from bone marrow may act as key effectors of the endometrial ASC niche.
  • 1.1K
  • 29 Apr 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).
  • 1.1K
  • 29 Mar 2022
Topic Review
Redox-Regulation of α-Globin in Vascular Physiology
Interest in the structure, function, and evolutionary relations of circulating and intracellular globins dates back more than 60 years to the first determination of the three-dimensional structure of these proteins. Non-erythrocytic globins have been implicated in circulatory control through reactions that couple nitric oxide (NO) signaling with cellular oxygen availability and redox status. Small artery endothelial cells (ECs) express free α-globin, which causes vasoconstriction by degrading NO. This reaction converts reduced (Fe2+) α-globin to the oxidized (Fe3+) form, which is unstable, cytotoxic, and unable to degrade NO. Therefore, (Fe3+) α-globin must be stabilized and recycled to (Fe2+) α-globin to reinitiate the catalytic cycle. The molecular chaperone α-hemoglobin-stabilizing protein (AHSP) binds (Fe3+) α-globin to inhibit its degradation and facilitate its reduction. The mechanisms that reduce (Fe3+) α-globin in ECs are unknown, although endothelial nitric oxide synthase (eNOS) and cytochrome b5 reductase (CyB5R3) with cytochrome b5 type A (CyB5a) can reduce (Fe3+) α-globin in solution.
  • 1.1K
  • 28 Jan 2022
Topic Review
Microalgae in Therapeutic Glycoproteins against SARS-CoV-2 Variants
SARS-CoV-2 mainly targets the respiratory tract, resulting in rapid and severe respiratory symptoms and lung failure, as well as some clinical symptoms such as fever, dry cough, fatigue, and dyspnea. In addition, studies reported gastrointestinal disturbances such as loss of appetite followed by diarrhea, nausea, and abdominal pain in the infected patients. Indeed, SARS-CoV-2 can also acutely replicate in the mucosa of the patient’s small intestine and excrete its RNA into the patient’s stool. In addition to these manifestations, many patients have exhibited a variety of symptoms (e.g., olfactory and gustatory disturbances, anosmia, headache, dysgeusia, confusion, and fatigue), which could be attributed to cranial nerve involvement. SARS-CoV-2, as with other coronaviruses, may initially invade peripheral-nerve endings and then progress regularly to the central nervous system via synaptic-connected junctions. Microalgae are eukaryotic, microscopic, and photosynthetic lower organisms that have recently been considered a more promising platform for the production of various biologics, especially complex glycosylated proteins.
  • 1.1K
  • 07 Nov 2022
Topic Review
Natural Killer Cell
NK cells are a group of innate immune cells that show spontaneous cytolytic activity against cells under stress, such as virus-infected cells and tumor cells. They belong to the innate lymphoid cells (ILCs) family, a recently discovered group of lymphocytes, and represent about 5–15% of human peripheral blood mononuclear cells (PBMCs). Except for directly killing target cell through the release of perforin- and granzyme-containing cytotoxic granules, NK cells can also secrete interferon (IFN-γ), tumor necrosis factor (TNF), the granulocyte–macrophage colony-stimulating factor (GM-CSF), and a panel of various immunoregulatory cytokines (IL-5, IL-10, IL-13) and chemokines (CCL-3, CCL-4, CCL-5, CXCL), by which they act as modulators of the inflammatory response. NK cells have recently been recognized for their ability to kill malignant or infected cells and maintain immune homeostasis by killing certain healthy immune cells [6]. Likewise, there is accumulating evidence that NK cells possess memory ability. This finding is in contrast to the classical definition of NK cells, by which they belong only in innate immunity cells due to their lack of RAG (Recombination-activating gene) recombinase-dependent clonal antigen receptors. New data suggest that two types of immune memory patterns can be found in NK cells. The first pattern, similarly to B and T cells, is achieved by exerting immunological memory after an encounter with various antigens and the consequent creation of generations of antigen-specific memory NK cells. Secondly, NK cells can remember inflammatory cytokines milieus that imprint long-lasting non-antigen-specific NK cell effector function. These findings of NK cells’ memory could open new horizons in their manipulation and provide us with new therapeutic targets, for example in ischemic heart disease, world's most notorious killer.
  • 1.1K
  • 29 Mar 2021
Topic Review
Epoetin Alfa
Epoetin alfa is a human erythropoietin produced in cell culture using recombinant DNA technology. Authorised by the European Medicines Agency on 28 August 2007, it stimulates erythropoiesis (increasing red blood cell levels) and is used to treat anemia, commonly associated with chronic kidney failure and cancer chemotherapy. Epoetin is manufactured and marketed by Amgen under the brand name Epogen. Johnson & Johnson subsidiary Janssen Biotech (formerly Ortho Biotech Products, LP), sells the same drug under the name Procrit, pursuant to a product license agreement. The average cost per patient in the U.S. was $8,447 in 2009. Darbepoetin alfa (rINN) /dɑːrbəˈpɔɪtɪn/ is a glycosylation analog of erythropoietin containing two additional N-linked carbohydrate chains, also manufactured and marketed by Amgen, with a brand name of Aranesp. The Food and Drug Administration (FDA) warnings and safety precautions for Procrit, Epogen and Aranesp are identical. For several years, epoetin alfa has accounted for the single greatest drug expenditure paid by the U.S. Medicare system; in 2010, the program paid $2 billion for the drug. Raising hemoglobin levels has been found in some studies to be associated with higher risks of thrombotic events, strokes and death. It is on the World Health Organization's List of Essential Medicines.
  • 1.1K
  • 01 Nov 2022
Topic Review
Mitochondrial Redox Signaling in Pulmonary Hypertension
Mitochondria are important organelles that act as a primary site to produce reactive oxygen species (ROS). Additionally, mitochondria play a pivotal role in the regulation of Ca2+ signaling, fatty acid oxidation, and ketone synthesis. Dysfunction of these signaling molecules leads to the development of pulmonary hypertension (PH), atherosclerosis, and other vascular diseases. Features of PH include vasoconstriction and pulmonary artery (PA) remodeling, which can result from abnormal proliferation, apoptosis, and migration of PA smooth muscle cells (PASMCs). These responses are mediated by increased Rieske iron–sulfur protein (RISP)-dependent mitochondrial ROS production and increased mitochondrial Ca2+ levels. Mitochondrial ROS and Ca2+ can both synergistically activate nuclear factor κB (NF-κB) to trigger inflammatory responses leading to PH, right ventricular failure, and death. 
  • 1.1K
  • 04 Jul 2022
Topic Review
Prokineticins and Prokineticin Receptors
Prokineticins are a new class of chemokine-like peptides involved in a wide range of biological and pathological activities. In particular, prokineticin 2 (PK2), prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2) play a central role in modulating neuroinflammatory processes. PK2 and PKRs, which are physiologically expressed at very low levels, are strongly upregulated during inflammation and regulate neuronal-glial interaction.
  • 1.1K
  • 18 Feb 2022
Topic Review
Ribosomal Gene Loci
Nucleoli form around actively transcribed ribosomal RNA (rRNA) genes (rDNA), and the morphology and location of nucleolus-associated genomic domains (NADs) are linked to the RNA Polymerase I (Pol I) transcription status. The number of rDNA repeats (and the proportion of actively transcribed rRNA genes) is variable between cell types, individuals and disease state. Substantial changes in nucleolar morphology and size accompanied by concomitant changes in the Pol I transcription rate have long been documented during normal cell cycle progression, development and malignant transformation. 
  • 1.1K
  • 29 Jul 2021
Topic Review
Dysregulation of miRNA in Leukemia
Micro RNAs (miRNAs) are a class of small non-coding RNAs that have a crucial role in cellular processes such as differentiation, proliferation, migration, and apoptosis. miRNAs may act as oncogenes or tumor suppressors; therefore, they prevent or promote tumorigenesis, and abnormal expression has been reported in many malignancies. The role of miRNA in leukemia pathogenesis is still emerging, but several studies have suggested using miRNA expression profiles as biomarkers for diagnosis, prognosis, and response to therapy in leukemia.
  • 1.1K
  • 29 Oct 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. 
  • 1.1K
  • 03 Nov 2022
Topic Review
Cytoplasmic Functions of cIAP1
Cellular inhibitor of apoptosis 1 (cIAP1) is a cell signaling regulator of the IAP family. Through its E3-ubiquitine ligase activity, it has the ability to activate intracellular signaling pathways, modify signal transduction pathways by changing protein-protein interaction networks, and stop signal transduction by promoting the degradation of critical components of signaling pathways. Thus, cIAP1 appears to be a potent determinant of the response of cells, enabling their rapid adaptation to changing environmental conditions or intra- or extracellular stresses. It is expressed in almost all tissues, found in the cytoplasm, membrane and/or nucleus of cells. cIAP1 regulates innate immunity by controlling signaling pathways mediated by tumor necrosis factor receptor superfamily (TNFRs), some cytokine receptors and pattern recognition-receptors (PRRs). Although less documented, cIAP1 has also been involved in the regulation of cell migration and in the control of transcriptional programs. 
  • 1.1K
  • 18 Mar 2022
Topic Review
Types of Senescent Cells in Cardiovascular Diseases
Senescent cell accumulation has been observed in age-associated diseases including cardiovascular diseases. Senescent cells lack proliferative capacity and secrete senescence-associated secretory phenotype (SASP) factors that may cause or worsen many cardiovascular diseases. Therapies targeting senescent cells, especially senolytic drugs that selectively induce senescent cell removal, have been shown to delay, prevent, alleviate, or treat multiple age-associated diseases in preclinical models. 
  • 1.1K
  • 12 May 2023
Topic Review
WWOX Controls Cell Survival, Immune Response, Disease Progression
Tumor suppressor WWOX inhibits cancer growth and retards Alzheimer’s disease (AD) progression. Supporting evidence shows that the more strongly WWOX binds intracellular protein partners, the weaker is cancer cell growth in vivo. Whether this correlates with retardation of AD progression is unknown. Two functional forms of WWOX exhibit opposite functions. pY33-WWOX is proapoptotic and anticancer, and is essential for maintaining normal physiology. 
  • 1.1K
  • 14 Jul 2022
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