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Topic Review
INOS in Ovarian Cancer
Inducible nitric oxide synthase (iNOS), the enzyme responsible for nitric oxide (NO) production, is not present in most cells under normal conditions. The expression of its mRNA, as well as its protein synthesis and full enzymatic activity, undergoes multilevel regulation including transcriptional and posttranscriptional mechanisms, the availability of iNOS substrate and cofactors and oxygen tension.
  • 1.4K
  • 22 Dec 2021
Topic Review
Immunological Synapse and Primary Cilium
The primary cilium is a small microtubule-based organelle that extends from the apical surface of most eukaryotic cells into the extracellular space for sensing and transducing a wide range of cues. Defects in cilia growth and function are associated with a group of human inherited multisystemic diseases, known as ciliopathies. In recent years a rising number of ciliary proteins have been described at extraciliary sites, both in ciliated and non-ciliated cells, and have been implicated in cilium-independent functions and different cellular processes. Hematopoietic cells, including T lymphocytes, do not form primary cilia. However, non-ciliated T cells co-opt the ciliogenesis machinery for the assembly and function of the immunological synapse, a well-organized structure formed by immune cells – multiple types of T cells, mast cells, NK cells, B cells, neutrophils, macrophages, and dendritic cells – allowing for antigen recognition and signaling, information exchange and polarized release of molecules into the synaptic cleft. The identification of many, unexpected similarities between the primary cilium and the T cell immunological synapse at the structural, functional and molecular levels have highlighted the homology between these structures, even though they show disparate morphologies. 
  • 1.4K
  • 11 Apr 2022
Topic Review
Dynamic Cancer Cell Heterogeneity
Though heterogeneity of cancers is recognized and has been much discussed in recent years, the concept often remains overlooked in different routine examinations. Indeed, in clinical or biological articles, reviews, and textbooks, cancers and cancer cells are generally presented as evolving distinct entities rather than as an independent heterogeneous cooperative cell population with its self-oriented biology. There are, therefore, conceptual gaps which can mislead the interpretations/diagnostic and therapeutic approaches.
  • 1.4K
  • 07 Feb 2022
Topic Review
Graviperception and Graviresponses in Euglena gracilis
The genus Euglena contains unicellular eukaryotic flagellates. In addition to light and chemicals, the cells perceive the gravitational field of the Earth and orient themselves paralell to the gravivector to optimize their position in the water column. The perception is based on transient receptor proteins in the membrane which are stimulated by the pressure of the cell content onto the lower membrane. Upon stimulation these proteins open and allow the influx of calcium from the outer medium which binds to a specific calmodulin. In turn this enzyme activates a adenylyl cyclase which produces cAMP believed to stimulate a phosphodiesterase A which finally modifies a flagellar protein which results in a course correction. Since Euglena is photosynthetic it absorbs carbon dioxide and produces oxygen and is thus an excellent candidate for a bioregenerative life support system during long-term space flights.
  • 1.4K
  • 04 Nov 2022
Topic Review
Age-Related Alterations at Neuromuscular Junction
With advancing aging, a decline in physical abilities occurs, leading to reduced mobility and loss of independence. Although many factors contribute to the physio-pathological effects of aging, an important event seems to be related to the compromised integrity of the neuromuscular system, which connects the brain and skeletal muscles via motoneurons and the neuromuscular junctions (NMJs). NMJs undergo severe functional, morphological, and molecular alterations during aging and ultimately degenerate. The effect of this decline is an inexorable decrease in skeletal muscle mass and strength, a condition generally known as sarcopenia. Moreover, several studies have highlighted how the age-related alteration of reactive oxygen species (ROS) homeostasis can contribute to changes in the neuromuscular junction morphology and stability, leading to the reduction in fiber number and innervation. Increasing evidence supports the involvement of epigenetic modifications in age-dependent alterations of the NMJ. In particular, DNA methylation, histone modifications, and miRNA-dependent gene expression represent the major epigenetic mechanisms that play a crucial role in NMJ remodeling. It is established that environmental and lifestyle factors, such as physical exercise and nutrition that are susceptible to change during aging, can modulate epigenetic phenomena and attenuate the age-related NMJs changes.
  • 1.4K
  • 15 Jun 2021
Topic Review
Subcellular Localization of Membrane-Type-1 Matrix Metalloproteinase
Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Membrane-type-1 matrix metalloproteinase (MT1-MMP), a transmembrane protein, is first known to localize to the cell membrane.
  • 1.4K
  • 15 Sep 2022
Topic Review
Tunneling Nanotubes
Tunneling nanotubes (TNTs) are recognized long membrane nanotubes connecting distance cells. In the last decade, growing evidence has shown that these subcellular structures mediate the specific transfer of cellular materials, pathogens, and electrical signals between cells. As intercellular bridges, they play a unique role in embryonic development, collective cell migration, injured cell recovery, cancer treatment resistance, and pathogen propagation. Although TNTs have been considered as potential drug targets for treatment, there is still a long way to go to translate the research findings into clinical practice.
  • 1.4K
  • 10 Mar 2021
Topic Review
Targeting CDK9 for Glioblastoma Treatment
Glioblastoma is the most common and aggressive primary malignant brain tumor, and more than two-thirds of patients with glioblastoma die within two years of diagnosis. The challenges of treating this disease mainly include genetic and microenvironmental features that often render the tumor resistant to treatments. Despite extensive research efforts, only a small number of drugs tested in clinical trials have become therapies for patients. Targeting cyclin-dependent kinase 9 (CDK9) is an emerging therapeutic approach that has the potential to overcome the challenges in glioblastoma management.
  • 1.4K
  • 02 Jul 2021
Topic Review
Scribble Polarity Module in Neuroblasts
The Scribble polarity module is composed by Scribble (Scrib), Discs large 1 (Dlg1) and Lethal (2) giant larvae (L(2)gl), a group of highly conserved neoplastic tumor suppressor genes (TSGs) from flies to humans. Even though the Scribble module has been profusely studied in epithelial cell polarity, the number of tissues and processes in which it is involved is increasingly growing. Here we discuss the role of the Scribble module in the asymmetric division of Drosophila neuroblasts (NBs), as well as the underlying mechanisms by which those TSGs act in this process. Finally, we also describe what we know about the consequences of mutating these genes in impairing the process of asymmetric NB division and promoting tumor-like overgrowth.
  • 1.4K
  • 29 Oct 2020
Topic Review
MOB
The MOB family proteins are constituted by highly conserved eukaryote kinase signal adaptors involved in the regulation of cell cycle progression, cell proliferation versus proliferation, morphogenesis, and cell differentiation and are often essential both for cell and organism survival.
  • 1.4K
  • 19 Jan 2021
Topic Review
LPA 3 Promotes Mitochondrial Homeostasis against Oxidative Stress
Lysophosphatidic acid (LPA) is a growth factor-like lipid mediator that regulates various physiological functions via activation of multiple LPA G protein-coupled receptors. Mitochondria have been suggested to be the primary origin of oxidative stress via the overproduction of reactive oxygen species (ROS). Mitochondria are responsible for producing ATP through oxidative phosphorylation (OXPHOS) and have a calcium buffering capacity for the cell. Defects in mitochondria will lead to declined antioxidant capacity and cell apoptosis. siRNA-mediated depletion of LPA3 leads to the depolarization of mitochondrial potential (ΔΨm) and cellular ROS accumulation. In addition, the depletion of LPA3 enhances cisplatin-induced cytochrome C releasing. This indicates that LPA3 is essential to suppress the mitochondrial apoptosis pathway. LPA3 is also shown to improve mitochondrial ADP-ATP exchange by enhancing the protein level of ANT2. On the other hand, LPA3 regulates calcium uptake from the ER to mitochondria via the IP3R1-VDAC1 channel. Moreover, activation of LPA3 by selective agonist OMPT rescues mitochondrial homeostasis of H2O2-induced oxidative stress cells and HGPS patient fibroblasts by improving mitochondrial ΔΨm and OXPHOS. 
  • 1.4K
  • 01 Apr 2022
Topic Review
Neuron–Glia Interaction in ENS
The enteric nervous system (ENS) constitutes the largest part of the peripheral nervous system.
  • 1.4K
  • 19 Jan 2021
Topic Review
Exosomes in Motor Neurone Disease
Exosomes are attractive as vehicle systems for small therapeutic molecules and/or biomolecules including nucleic acids and proteins because of their lipid nature, presence of specific surface ligands (CD11b and CD18 receptors, integrins, tetraspanins) and ability to cross the blood–brain barrier. When compared to other drug delivery systems, exosomes have the distinct advantages of blood–brain barrier penetrance, longer duration in systemic circulation, tissue specificity that minimizes unwanted toxicity or off-target effects, stability of content, desirable biocompatibility and minimal toxicity issues. Techniques such as fusion expression, exosome membrane surface display and anchoring platforms have been used to attach peptides and biological ligands of interest to adhesion molecules, tetraspanins or integrins on exosome surface to ensure targeted delivery and enhanced uptake into desired cells.
  • 1.4K
  • 08 Nov 2021
Topic Review
CIDE Proteins in Human Health
Cell death-Inducing DNA Fragmentation Factor Alpha (DFFA)-like Effector (CIDE) proteins have emerged as lipid droplet-associated proteins that regulate fat metabolism. There are three members in the CIDE protein family—CIDEA, CIDEB, and CIDEC (also known as fat-specific protein 27 (FSP27)). CIDEA and FSP27 are primarily expressed in adipose tissue, while CIDEB is expressed in the liver. Originally, based upon their homology with DNA fragmentation factors, these proteins were identified as apoptotic proteins. However, recent studies have changed the perception of these proteins, redefining them as regulators of lipid droplet dynamics and fat metabolism, which contribute to a healthy metabolic phenotype in humans. Despite various studies in humans and gene-targeting studies in mice, the physiological roles of CIDE proteins remains elusive.
  • 1.4K
  • 07 Jun 2022
Topic Review
Membrane Remodeling by ESCRTs
The endosomal sorting complex required for transport (ESCRT) machinery is an evolutionarily conserved membrane remodeling complex that is used by the cell to perform reverse membrane scission in essential processes like protein degradation, cell division, and release of enveloped retroviruses. ESCRT-III, together with the AAA ATPase VPS4, harbors the main remodeling and scission function of the ESCRT machinery, whereas early-acting ESCRTs mainly contribute to protein sorting and ESCRT-III recruitment through association with upstream targeting factors.
  • 1.4K
  • 01 Jul 2022
Topic Review
Functional Roles of ISG15/ISGylation in Cancer
The protein ISG15 encoded by interferon-stimulated gene (ISG) 15 is the first identified member of the ubiquitin-like protein family and exists in the form of monomers and conjugated complexes. Like ubiquitin, ISG15 can mediate an ubiquitin-like modification by covalently modifying other proteins, known as ISGylation. There is growing evidence showing that both the free and conjugated ISG15 are involved in multiple key cellular processes, including autophagy, exosome secretion, DNA repair, immune regulation, and cancer occurrence and progression.
  • 1.4K
  • 17 Feb 2023
Topic Review
Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation
KRAS, one of the RAS protein family members, plays an important role in autophagy and apoptosis, through the regulation of several downstream effectors. In cancer cells, KRAS mutations confer the constitutive activation of this oncogene, stimulating cell proliferation, inducing autophagy, suppressing apoptosis, altering cell metabolism, changing cell motility and invasion and modulating the tumor microenvironment.
  • 1.4K
  • 21 Jul 2022
Topic Review
3D Cell Culture in Micro-Bioreactors
Bioreactors have proven useful for a vast amount of applications. Besides classical large-scale bioreactors and fermenters for prokaryotic and eukaryotic organisms, micro-bioreactors, as specialized bioreactor systems, have become an invaluable tool for mammalian 3D cell cultures. 
  • 1.4K
  • 27 Jan 2021
Topic Review
HSP70 in Cancer
The 70-kDa heat shock proteins (HSP70s) are abundantly present in cancer, providing malignant cells selective advantage by suppressing multiple apoptotic pathways, regulating necrosis, bypassing cellular senescence program, interfering with tumor immunity, promoting angiogenesis and supporting metastasis. This direct involvement of HSP70 in most of the cancer hallmarks explains the phenomenon of cancer “addiction” to HSP70, tightly linking tumor survival and growth to the HSP70 expression. HSP70 operates in different states through its catalytic cycle, suggesting that it can multi-function in malignant cells in any of these states. Clinically, tumor cells intensively release HSP70 in extracellular microenvironment, resulting in diverse outcomes for patient survival. Given its clinical significance, small molecule inhibitors were developed to target different sites of the HSP70 machinery. Furthermore, several HSP70-based immunotherapy approaches were assessed in clinical trials.
  • 1.4K
  • 19 May 2021
Topic Review
In Vitro Models of Immune Dysfunction in Space
Spaceflight affects the body on every level. Reports on astronaut health identify bone marrow remodelling and dysfunction of the innate immune system as significant health risks of long-term habitation in space. Microgravity-induced alterations of the bone marrow induce physical changes to the bone marrow stem cell niche. Downstream effects on innate immunity are expected due to impaired hematopoiesis and myelopoiesis. To date, few studies have investigated these effects in real microgravity and the sparsely available literature often reports contrasting results. This emphasizes a need for the development of physiologically relevant in vitro models of the bone marrow stem cell niche, capable of delivering appropriate sample sizes for robust statistics.
  • 1.4K
  • 07 Apr 2022
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