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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
Flipons and Condensates Enhances Evolution
A number of insights derive from viewing flipons as scaffolds for condensates. Flipons provide a controlled way to initiate condensate formation, one subject to natural selection. The alternative conformation localizes required factors needed to regulate transcription, RNA processing, and epigenetic modification, while excluding nucleosomes and other B-DNA- and A-RNA-specific proteins that produce competing outcomes.
  • 1.1K
  • 22 Sep 2021
Topic Review Peer Reviewed
Biotechnology and Cytotherapeutics:The Swiss Progenitor-Cell Transplantation Program
Historically, primary human progenitor cells (e.g., WI-38 and MRC-5 diploid-cell sources) have been industrially applied in research and in manufacturing processes for vaccines and for biologicals. Furthermore, tissue-specific primary progenitor-cell banks have recently been developed and exploited for the provision of safe, consistent, and effective cellular active pharmaceutical ingredients (API) in homologous allogeneic regenerative medicine applications. Notably, the modern legal and regulatory frameworks for novel therapeutic products and for progenitor-cell therapy development have been iteratively optimized to guarantee utmost product safety, quality, and efficacy. Over 50 years of global technical hindsight around progenitor-cell biotechnological substrates and over 30 years of in-house clinical experience around the therapeutic uses of standardized progenitor-cell sources in Switzerland have demonstrated the importance of such biological materials for public health. The aim of this entry work was to summarize the evolution of the industrial applications of selected primary progenitor-cell sources, ranging from the use as robust biotechnological substrates to standardized cellular API manufacture and their clinical uses in highly specialized regenerative medicine.
  • 1.1K
  • 18 Apr 2022
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
Myofibroblasts
Myofibroblasts are contractile, α-smooth muscle actin-positive cells with multiple roles in pathophysiological processes. Myofibroblasts mediate wound contractions, but their persistent presence in tissues is central to driving fibrosis, making them attractive cell targets for the development of therapeutic treatments. However, due to shared cellular markers with several other phenotypes, the specific targeting of myofibroblasts has long presented a scientific and clinical challenge.
  • 1.1K
  • 11 Aug 2023
Topic Review
Calcitonin Gene-Related Peptide and Bone Repair
Calcitonin gene-related peptide (CGRP) has 37 amino acids. Initially, CGRP had vasodilatory and nociceptive effects. As research progressed, evidence revealed that the peripheral nervous system is closely associated with bone metabolism, osteogenesis, and bone remodeling. Thus, CGRP is the bridge between the nervous system and the skeletal muscle system. CGRP can promote osteogenesis, inhibit bone resorption, promote vascular growth, and regulate the immune microenvironment. The G protein-coupled pathway is vital for its effects, while MAPK, Hippo, NF-κB, and other pathways have signal crosstalk, affecting cell proliferation and differentiation. 
  • 1.1K
  • 31 May 2023
Topic Review
Oxygen Homeostasis
The unique biology of the intestinal epithelial barrier is linked to a low baseline oxygen pressure (pO2), characterised by a high rate of metabolites circulating through the intestinal blood and the presence of a steep oxygen gradient across the epithelial surface. These characteristics require tight regulation of oxygen homeostasis, achieved in part by hypoxia-inducible factor (HIF)-dependent signalling. Furthermore, intestinal epithelial cells (IEC) possess metabolic identities that are reflected in changes in mitochondrial function. In recent years, it has become widely accepted that oxygen metabolism is key to homeostasis at the mucosae. In addition, the gut has a vast and diverse microbial population, the microbiota. Microbiome–gut communication represents a dynamic exchange of mediators produced by bacterial and intestinal metabolism. The microbiome contributes to the maintenance of the hypoxic environment, which is critical for nutrient absorption, intestinal barrier function, and innate and/or adaptive immune responses in the gastrointestinal tract.
  • 1.1K
  • 22 Sep 2021
Topic Review
Dietary Antioxidants in Age-Related Macular Degeneration and Glaucoma
Age-related macular degeneration (AMD) and glaucoma are ophthalmic neurodegenerative diseases responsible for irreversible vision loss in the world population. Only a few therapies can be used to slow down the progression of these diseases and there are no available treatment strategies for reversing the degeneration of the neural retina. In AMD, the pathological process causes the malfunction and damage of the retinal pigmented epithelium and photoreceptors in the macula. In glaucoma, damage of the retinal ganglion cells and their axons is observed and treatment strategies are limited to intraocular pressure lowering. Therefore, other prophylactic and/or therapeutic methods are needed. Oxidative stress is involved in the neurodegenerative process accompanying both AMD and glaucoma; therefore, the use of antioxidant agents would clearly be beneficial, which is supported by the decreased prevalence and progression of AMD in patients adherent to a diet naturally rich in antioxidants.
  • 1.1K
  • 11 Nov 2021
Topic Review
Epigenetic Changes and Chromatin Reorganization in Brain Function
Healthy brain functioning in mammals requires a continuous fine-tuning of gene expression. Accumulating evidence over the past demonstrates that epigenetic mechanisms and dynamic changes in chromatin organization are critical components during the control of gene transcription in neural cells. Genome-wide analyses show that the regulation of brain genes requires the contribution of both promoter and long-distance enhancer elements, which must functionally interact to upregulate gene expression in response to physiological cues. Hence, a deep comprehension of the mechanisms mediating these enhancer–promoter interactions (EPIs) is critical if people are to understand the processes associated with learning, memory and recall. Moreover, the onset and progression of several neurodegenerative diseases and neurological alterations are found to be strongly associated with changes in the components that support and/or modulate the dynamics of these EPIs. 
  • 1.1K
  • 28 Oct 2022
Topic Review
Possible Role of Kiss1/GPR54 System in Skeletal Muscle
The skeletal muscle is the storage organ for muscle glycogen and the most prominent motor organ of an organism. Consequently, the relationship between the skeletal muscle and energy metabolism cannot be ignored during physical activities, especially during exercise. The Kiss1/GPR54 system is a multifunctional genetic system with an essential role in regulating energy balance and metabolic homeostasis. Expression of Kiss1 and GPR54 mRNAs can be detected in skeletal muscle of some mammals. However, the Kiss1/GPR54 system in skeletal muscles has not been thoroughly studied. Researchers have proposed the speculation on the possible role of the kiss1 /GPRS4 system in skeletal muscle in association with exercise performance.
  • 1.1K
  • 18 Nov 2022
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
Nuclei-Based Methods on Next-Generation Sequencing
Nuclei-based methods have become increasingly popular in the study of gene expression, epigenetics, and chromatin structure. To ensure the acquisition of biologically meaningful data, it is important to consider the available methodologies, future direction, and potential challenges and utilize improved designs and appropriate experimental strategies.
  • 1.1K
  • 21 Apr 2023
Topic Review
Engineering Extracellular Vesicles for Targeted Drug Delivery
Extracellular vesicles (EVs) are membranous nanosized particles produced by nearly all cell types, including eukaryotic and prokaryotic cells, and they carry their parent cell’s cytosolic components in their lumen, including RNA and various proteins. EVs can be broadly classified into three types by their biogenesis pathway: exosomes, microvesicles (ectosomes) and apoptotic bodies. EVs can be decorated with surface molecules to enhance their targeting abilities. This can be accomplished by directly attaching targeting moieties to the EV surface or modifying EV-producing cells.
  • 1.1K
  • 27 Sep 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
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
Assessing Myocardial Architecture
Myocardial architecture and cardiac function are closely linked. Hence, the anatomy of the heart and the cellular construction of the myocardium has been the focus of research for centuries. Traditionally, histology has been the method of choice, but owing to its two-dimensional nature, this technique fails to visualise the myocardial mass in its entirety. It has long been recognised that the myocardium is a highly complex three-dimensional syncytium, thus it is preferable to investigate its architecture using tools capable of representing this three-dimensionality. Such tools have been provided in the shape of diffusion tensor imaging, computed tomography, confocal microscopy and ultrasound, with diffusion tensor imaging and computed tomography being the most prevalent and valid methods for quantifying myocardial architecture in three dimensions.
  • 1.1K
  • 04 Dec 2020
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
Histone Variants in Epithelial-To-Mesenchymal Transition
The epithelial-to-mesenchymal transition (EMT) is a physiological process activated during early embryogenesis, which continues to shape tissues and organs later on. It is also hijacked by tumor cells during metastasis. The regulation of EMT has been the focus of many research groups culminating in the last few years and resulting in an elaborate transcriptional network buildup. Recent discoveries pointed out that histone variants, which are key epigenetic players, appear to be involved in EMT control. 
  • 1.1K
  • 03 Jan 2021
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
Store-Operated Calcium Entry in Cancer Stem Cells
Store-Operated Calcium Entry (SOCE), a major mechanism for Ca2+influx from the extracellular medium into excitable and non-excitable cells, is physiologically triggered by the activation of phospholipase C (PLC) and the production of IP3, which subsequently leads to the release of Ca2+from intracellular stores, mainly the ER, resulting in the activation of store-operated calcium channels in the plasma membrane and a rapid increase in cytosolic Ca2+concentration. SOCE is an extremely complex biological mechanism, with high dependency on the pattern of expression of its components-STIMs, Orai, and TRPC proteins- and its modulators in each cell type. Since the last decades of the 20th century, several studies, both in vivo and in vitro, have reported that an altered expression pattern of the proteins that mediate SOCE leads to unbalanced Ca2+homeostasis, which might contribute to tumor development, poor prognosis, and chemotherapeutic drug resistance.
  • 1.1K
  • 29 Apr 2022
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