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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
Cyclin-Dependent Inhibitors in Diet-Induced Obesity and Cancer
Overweight and obesity constitute the most impactful lifestyle-dependent risk factors for cancer and have been tightly linked to a higher number of tumor-related deaths nowadays. The excessive accumulation of energy can lead to an imbalance in the level of essential cellular biomolecules that may result in inflammation and cell-cycle dysregulation. Nutritional strategies and phytochemicals are gaining interest in the management of obesity-related cancers, with several ongoing and completed clinical studies that support their effectiveness. At the same time, cyclin-dependent kinases (CDKs) are becoming an important target in breast and ovarian cancer treatment, with various FDA-approved CDK4/6 inhibitors that have recently received more attention for their potential role in diet-induced obesity (DIO).
  • 1.1K
  • 10 Jun 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
Cell Mechanics in Embryoid Bodies
Embryoid bodies (EBs) resemble self-organizing aggregates of pluripotent stem cells that recapitulate some aspects of early embryogenesis. Within few days, the cells undergo a transition from rather homogeneous epithelial-like pluripotent stem cell colonies into a three-dimensional organization of various cell types with multifaceted cell–cell interactions and lumen formation—a process associated with repetitive epithelial-mesenchymal transitions. In the last few years, culture methods have further evolved to better control EB size, growth, cellular composition, and organization—e.g., by the addition of morphogens or different extracellular matrix molecules. There is a growing perception that the mechanical properties, cell mechanics, and cell signaling during EB development are also influenced by physical cues to better guide lineage specification; substrate elasticity and topography are relevant, as well as shear stress and mechanical strain. Epithelial structures outside and inside EBs support the integrity of the cell aggregates and counteract mechanical stress. Furthermore, hydrogels can be used to better control the organization and lineage-specific differentiation of EBs. In this review, we summarize how EB formation is accompanied by a variety of biomechanical parameters that need to be considered for the directed and reproducible self-organization of early cell fate decisions.
  • 1.1K
  • 08 Oct 2021
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
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
Natural Killer Cell-Derived Extracellular Vesicles for Cancer
Cancer is the second leading contributor to global deaths caused by non-communicable diseases. The cancer cells are known to interact with the surrounding non-cancerous cells, including the immune cells and stromal cells, within the tumor microenvironment (TME) to modulate the tumor progression, metastasis and resistance. Chemotherapy and radiotherapy are the standard treatments for cancers. A new generation of immunotherapy using natural killer (NK) cells, cytotoxic CD8+ T-lymphocytes or macrophages was developed to achieve tumor-specific targeting and circumvent the adverse effects.
  • 1.1K
  • 21 Feb 2023
Topic Review
Breakdown of Filamentous Myofibrils
Protein degradation maintains cellular integrity by regulating virtually all biological pro- cesses, whereas impaired proteolysis perturbs protein quality control, and often leads to human disease. Two major proteolytic systems are responsible for protein breakdown in all cells: autophagy, which facilitates the loss of organelles, protein aggregates, and cell surface proteins; and the ubiquitin-proteasome system (UPS), which promotes degradation of mainly soluble proteins. Recent findings indicate that more complex protein structures, such as filamentous assemblies, which are not acces- sible to the catalytic core of the proteasome in vitro, can be efficiently degraded by this proteolytic machinery in systemic catabolic states in vivo. Mechanisms that loosen the filamentous structure seem to be activated first, hence increasing the accessibility of protein constituents to the UPS. In this review, we will discuss the mechanisms underlying the disassembly and loss of the intricate insoluble filamentous myofibrils, which are responsible for muscle contraction, and whose degradation by the UPS causes weakness and disability in aging and disease. Several lines of evidence indicate that myofibril breakdown occurs in a strictly ordered and controlled manner, and the function of AAA-ATPases is crucial for their disassembly and loss.
  • 1.1K
  • 30 Apr 2021
Topic Review
Stem Cells Radiation-Induced Regenerative Response
Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of normal tissues is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration.  
  • 1.1K
  • 03 Mar 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
NF-κB and Human Cancer
Transcription factor NF-κB has been extensively studied for its varied roles in cancer since its initial characterization as a potent retroviral oncogene several decades ago. It is now clear that NF-κB plays a major role in a large variety of human cancers, including especially ones of immune cell origin. NF-κB is generally constitutively or aberrantly activated in human cancers where it is involved.
  • 1.1K
  • 25 Dec 2021
Topic Review
Megakaryocytes in Brief
Megakaryocytes are large bone marrow cells responsible for producing platelets crucial for blood clotting. They undergo endomitosis, becoming polyploid to generate thousands of platelets. Beyond thrombopoiesis, they regulate hematopoietic niches and immune responses. Dysregulation can lead to disorders like thrombocytopenia, myeloproliferative neoplasms, and acute megakaryoblastic leukemia.
  • 1.1K
  • 26 Aug 2024
Topic Review
PDE2A for Mouse Liver Development
cAMP and cGMP are intracellular signaling molecules produced in response to a plethora of extracellular signals in order to coordinate cellular metabolism, proliferation, differentiation and apoptosis. Phosphodiesterases (PDEs) are the enzymes that hydrolyze cAMP and cGMP in order to end or to limit the responses to these signals. To date 11 PDE families (named PDE1 to PDE11) have been identified across each cell type expressed in a peculiar pattern. They enclose 21 genes that codify approximately 100 enzymes that form a redundant network ensuring the compensation of activity in case of alteration of activity or lack of expression of one of the members. PDE2A, a cAMP-hydrolyzing enzyme, represents the exception to this picture, as PDE2A knockout is embryonic lethal. Knockout embryos show that the lack of the enzyme has the greatest impact on the development of the heart and of the liver, which is no longer able to assume its hematopoietic role. The increase of the intracellular cAMP level and the downregulation of the anti-apoptotic gene Bcl2 might explain the loss of integrity in the PDE2A knockout liver niche that compromises the hematopoietic function and maturation.
  • 1.1K
  • 29 Oct 2020
Topic Review
ZBP1-Mediated Necroptosis
Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. 
  • 1.1K
  • 03 Jan 2023
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 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
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
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
Myostatin/Activin-A Signaling and Functions
Myostatin and activin-A are two of thirty-three members of the TGF-β family.
  • 1.1K
  • 31 Aug 2021
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