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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
Human In Vitro Stem Cell-Derived Models of Epilepsy
The challenges in making animal models of complex human epilepsy phenotypes with varied aetiology highlights the need to develop alternative disease models that can address the limitations of animal models by effectively recapitulating human pathophysiology. The advances in stem cell technology provide an opportunity to use human iPSCs to make disease-in-a-dish models.
  • 1.1K
  • 26 Dec 2022
Topic Review
Mesenchymal Stem Cells in COVID-19
Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells’ differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration.
  • 1.1K
  • 14 Oct 2021
Topic Review
Mitochondrial Volume Regulation and Swelling Mechanisms in Cardiomyocytes
Mitochondrion, known as the “powerhouse” of the cell, regulates ion homeostasis, redox state, cell proliferation and differentiation, and lipid synthesis. The inner mitochondrial membrane (IMM) controls mitochondrial metabolism and function. It possesses high levels of proteins that account for ~70% of the membrane mass and are involved in the electron transport chain, oxidative phosphorylation, energy transfer, and ion transport, among others. The mitochondrial matrix volume plays a crucial role in IMM remodeling. Several ion transport mechanisms, particularly K+ and Ca2+, regulate matrix volume. Small increases in matrix volume through IMM alterations can activate mitochondrial respiration, whereas excessive swelling can impair the IMM topology and initiates mitochondria-mediated cell death. The opening of mitochondrial permeability transition pores, the well-characterized phenomenon with unknown molecular identity, in low- and high-conductance modes are involved in physiological and pathological increases of matrix volume.
  • 1.1K
  • 10 Aug 2023
Topic Review
Senescent Microglia
Microglia, far from being simply ‘brain glue’, play an important role as the brain’s resident immune cells. Their roles include phagocytic clearance of debris, pruning of synapses, and possibly even contributing to synaptic activity, being of critical importance from early development to ageing. Despite being such long-lived cells, microglia have been relatively understudied for their role in the ageing process. Reliably identifying aged microglia has proven challenging, not least due to the diversity of cell populations, and the limitations of available models, further complicated by differences between human and rodent cells.
  • 1.1K
  • 07 May 2021
Topic Review
Peptide-Assisted Nucleic Acid Delivery Systems
Advances in peptide development have made peptide-assisted gene delivery more efficient in vitro and, in some instances, in small animal models. For example, cell and tissue selectivity could be greatly enhanced in the newest generation of CPPs. Other advances which allow for improved performance with regard to targeting and delivery of nucleic acids include adapting peptide sequences to facilitate escape or release from intracellular vesicles or respond to environmental stimuli for a controlled release of cargo, and the development of composite, multivalent peptide-based, or peptide-coupled structures.
  • 1.1K
  • 08 Sep 2021
Topic Review
Deciphering Tumour Heterogeneity
Decoding tumour heterogeneity is a major clinical challenge, considering that it immensely contributes to cancer progression, treatment failure and emergence of drug resistance. Emerging technical and sampling strategies have been developed in order to deeply characterise tumour complexity and clonal architecture, including single-cell profiling, multi-region sampling, representative sampling and longitudinal analysis of liquid biopsy samples.
  • 1.1K
  • 25 Mar 2022
Topic Review
Cd34+ Stromal Cells/Telocytes
CD34+ stromal cells/telocytes (CD34+SCs/TCs) are an important interstitial, perivascular, peri/endoneurial and periadnexal cellular component in the dermis and hypodermis (subcutaneous adipose tissue) of the skin. Most CD34+ stromal cells are known to correspond to telocytes, a new cellular type identified by electron microscopy.
  • 1.1K
  • 29 Jul 2021
Topic Review
Autophagy in Chronic Heart Failure
Autophagy is a conserved cell quality control system, and increasing evidence suggests that it plays an important role in numerous and different biological processes, such as starvation, aging, inflammation, and organ remodeling, by maintaining cellular homeostasis.
  • 1.1K
  • 14 Apr 2021
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. 
  • 1.1K
  • 27 Apr 2021
Topic Review
miRNAs in Learning, Memory, and Cognitive Disorders
Learning and memory formation rely on the precise spatiotemporal regulation of gene expression, such as microRNA (miRNA)-associated silencing, to fine-tune gene expression for the induction and maintenance of synaptic plasticity. Some of these are involved in well-known mechanisms, such as the CREB-dependent signaling pathway, and some of their roles are in fear- and stress-related disorders, particularly cognitive impairment.
  • 1.1K
  • 23 Aug 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
P2X7 Variants
The human P2X7 gene is highly polymorphic, and several splice variants of the receptor have been identified in time. P2X7 single-nucleotide polymorphisms (SNPs) have been broadly analyzed by studies relating them to pathologies as different as infectious, inflammatory, nervous, and bone diseases, among which cancer is included. Moreover, in the last years, an increasing number of reports concentrated on P2X7 splice variants’ different roles and their implications in pathological conditions, including oncogenesis. Our article on P2X7 variants in oncogenesis recently published in Cells gives an overview of established and recent literature demonstrating a role for human P2X7 gene products in oncological conditions. Here you find the main structural information on P2X7 variants.
  • 1.1K
  • 02 Feb 2021
Topic Review
Translation Impairment in Neurodegeneration
Protein synthesis is a strictly controlled molecular process because of its central role in different key cellular events, including homeostasis maintenance and response to extra- and intracellular cues. Increasing evidence suggests a dysfunction of the translation machinery in different neurodegenerative disorders. These dysfunctions are characterized by the accumulation of pathological protein aggregates, which could reflect defects in both ribosome and ribosome-associated activities.
  • 1.1K
  • 07 Dec 2022
Topic Review
Lipid-Based mRNA Nanoparticles
Messenger RNA (mRNA) is being extensively used in gene therapy and vaccination due to its safety over DNA, in the following ways: its lack of integration risk, cytoplasmic expression, and transient expression compatible with fine regulations. However, clinical applications of mRNA are limited by its fast degradation by nucleases, and the activation of detrimental immune responses. Advances in mRNA applications, with the recent approval of COVID-19 vaccines, were fueled by optimization of the mRNA sequence and the development of mRNA delivery systems. Although delivery systems and mRNA sequence optimization have been abundantly reviewed, understanding of the intracellular processing of mRNA is mandatory to improve its applications. 
  • 1.1K
  • 12 Jul 2021
Topic Review
Gallic Acid Activates KDM2A
KDM2A is a member of one group of α-ketoglutarate-dependent oxygenases. KDM2A in the rDNA promoter is activated by nutrient starvation, to reduce rRNA transcription and cell proliferation. While gallic acid functions as an antioxidant, gallic acid autoxidation also produces significant levels of reactive oxygen species (ROS). Gallic acid activates KDM2A to reduce rRNA transcription and cell proliferation in breast cancer MCF-7 cells but not in non-tumorous MCS10A cells. The activation of KDM2A by gallic acid depends on ROS production and AMPK activation.
  • 1.1K
  • 26 Oct 2020
Topic Review
FGF Signaling in Vertebrate Embryos
Fibroblast growth factors (FGFs) comprise a large family of growth factors, regulating diverse biological processes including cell proliferation, migration, and differentiation. Each FGF binds to a set of FGF receptors to initiate certain intracellular signaling molecules. Accumulated evidence suggests that in early development and adult state of vertebrates, FGFs also play exclusive and context dependent roles.
  • 1.1K
  • 08 Sep 2021
Topic Review
Dietary Modulation of Bacteriophages
The role and function of bacteriophages (phages) has been underestimated so far. Natural compounds such as essential oils and tea have been used successfully in naturopathy and folk medicine for hundreds of years. Current research is unveiling the molecular role of their antibacterial, anti-inflammatory, and anticancer properties. The current interdisciplinary review summarizes current knowledge on dietary compounds as to their capacity to modulate the activity of phages, thus potentially contributing to (the modulation of) several gastrointestinal diseases, such as (chronic) inflammation, and even cancer.
  • 1.1K
  • 27 Apr 2021
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
LRRK2 and Lipid Pathways
Genetic alterations in the LRRK2 gene, encoding leucine-rich repeat kinase 2, are a common risk factor for Parkinson’s disease. How LRRK2 alterations lead to cell pathology is an area of ongoing investigation, multiple lines of evidence suggest a role for LRRK2 in lipid pathways. It is increasingly recognized that in addition to being energy reservoirs and structural entities, some lipids, including neural lipids, participate in signaling cascades. Early investigations revealed that LRRK2 localized to membranous and vesicular structures, suggesting an interaction of LRRK2 and lipids or lipid-associated proteins. LRRK2 substrates from the Rab GTPase family play a critical role in vesicle trafficking, lipid metabolism and lipid storage, all processes which rely on lipid dynamics. In addition, LRRK2 is associated with the phosphorylation and activity of enzymes that catabolize plasma membrane and lysosomal lipids. Furthermore, LRRK2 knockout studies have revealed that blood, brain and urine exhibit lipid level changes, including alterations to sterols, sphingolipids and phospholipids, respectively. In human LRRK2 mutation carriers, changes to sterols, sphingolipids, phospholipids, fatty acyls and glycerolipids are reported in multiple tissues.
  • 1.1K
  • 19 Jan 2023
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