Nanoparticle shape is the game-changer for blood-brain barrier crossing and delivery through tunneling nanotubes among glioblastoma cells.

Tunneling nanotubes (TNTs) are thin, dynamic, long membrane protrusions that allow intercellular exchanges of signaling clues, molecules and organelles. The presence of TNTs and their involvement as drug delivery channels have been observed in several types of cancer, including glioblastoma. Recently, increased attention has been directed toward nanoparticles (NPs) that can be transported in TNTs.

Polyacrylic-Coated Solid Nanoparticles Increase the Aquaporin Permeability to Hydrogen Peroxide.

Aquaporins (AQPs) allow the diffusion of hydrogen peroxide (HO) and act as ROS scavenging systems, which are important for controlling the redox state of cells. Recently, cerium oxide nanoparticles were found to increase the water and HO permeability by modulating AQPs. To further analyze the action of nanoparticles (NPs) on AQP, we examined the effect of the NPs presenting different core compositions (CeO, GdO, FeO, and TiO), hydrodynamic sizes, and surface functionalization.

Synthesis and Characterization of Gd-Functionalized BC Nanoparticles for BNCT Applications.

Inorganic nanoparticles of boron-rich compounds represent an attractive alternative to boron-containing molecules, such as boronophenylalanine or boranes, for BNCT applications. This work describes the synthesis and biological activity of multifunctional boron carbide nanoparticles stabilized with polyacrylic acid (PAA) and a gadolinium ()-rich solid phase. A fluorophore (DiI) was included in the PAA functionalization, allowing the confocal microscopy imaging of the nanoparticles.

Cerium Oxide Nanoparticles Regulate Oxidative Stress in HeLa Cells by Increasing the Aquaporin-Mediated Hydrogen Peroxide Permeability.

Some aquaporins (AQPs) allow the diffusion of hydrogen peroxide (HO), the most abundant ROS, through the cell membranes. Therefore, the possibility of regulating the AQP-mediated permeability to HO, and thus ROS scavenging, appears particularly important for controlling the redox state of cells in physiological and pathophysiological conditions. Several compounds have been screened and characterized for this purpose.

Microvilli Adhesion: An Alternative Route for Nanoparticle Cell Internalization.

The cellular uptake of nanoparticles (NPs) represents a critical step in nanomedicine and a crucial point for understanding the interaction of nanomaterials with biological systems. No specific mechanism of uptake has been identified so far, as the NPs are generally incorporated by the cells through one of the few well-known endocytotic mechanisms. Here, an alternative internalization route mediated by microvilli adhesion is demonstrated.

Oxidative Stress Boosts the Uptake of Cerium Oxide Nanoparticles by Changing Brain Endothelium Microvilli Pattern.

Vascular oxidative stress is considered a worsening factor in the progression of Alzheimer's disease (AD). Increased reactive oxygen species (ROS) levels promote the accumulation of amyloid-β peptide (Aβ), one of the main hallmarks of AD. In turn, Aβ is a potent inducer of oxidative stress.

Colocalization of tracks from boron neutron capture reactions and images of isolated cells.

In Boron Neutron Capture Therapy, the boronated drug plays a leading role in delivering a lethal dose to the tumour. The effectiveness depends on the boron macroscopic concentration and on its distribution at sub-cellular level. This work shows a way to colocalize alpha particles and lithium ions tracks with cells.

CagA Effector Protein in -Infected Human Gastric Epithelium in Vivo: From Bacterial Core and Adhesion/Injection Clusters to Host Cell Proteasome-Rich Cytosol.

A key role in the carcinogenic action of is played by the effector protein CagA, the first identified oncoprotein of the bacterial world. However, the present knowledge in regard to the bacterial injection of CagA into epithelial cells (through a type IV secretion system) and its intracellular fate is based primarily on experimental studies in vitro. Our study was aimed to investigate, in -infected human gastric epithelium, CagA delivery and intracellular distribution in order to identify any in vivo counterpart of the cell injection mechanism described in vitro and any intracellular cytoplasmic site of preferential CagA distribution, thus shedding light on the natural history of CagA in vivo.

Proteasome-Rich PaCS as an Oncofetal UPS Structure Handling Cytosolic Polyubiquitinated Proteins. In Vivo Occurrence, in Vitro Induction, and Biological Role.

In this article, we outline and discuss available information on the cellular site and mechanism of proteasome interaction with cytosolic polyubiquitinated proteins and heat-shock molecules. The particulate cytoplasmic structure (PaCS) formed by barrel-like particles, closely reproducing in vivo the high-resolution structure of 26S proteasome as isolated in vitro, has been detected in a variety of fetal and neoplastic cells, from living tissue or cultured cell lines. Specific trophic factors and interleukins were found to induce PaCS during in vitro differentiation of dendritic, natural killer (NK), or megakaryoblastic cells, apparently through activation of the MAPK-ERK pathway.

Natural history of Helicobacter pylori VacA toxin in human gastric epithelium in vivo: vacuoles and beyond.

Uptake, intracellular trafficking and pathologic effects of VacA toxin from Helicobacter pylori have been widely investigated in vitro. However, no systematic analysis investigated VacA intracellular distribution and fate in H. pylori-infected human gastric epithelium in vivo, using ultrastructural immunocytochemistry that combines precise toxin localization with analysis of the overall cell ultrastructure and intercompartimental/interorganellar relationships.

Different Polyubiquitinated Bodies in Human Dendritic Cells: IL-4 Causes PaCS During Differentiation while LPS or IFNα Induces DALIS During Maturation.

Two types of polyubiquitin-reactive cytoplasmic bodies, particulate cytoplasmic structures (PaCS) and dendritic cell (DC) aggresome-like induced structures (DALIS), were analyzed by electron microscopy, immunocytochemistry, immunoblotting, and flow cytometry in DC obtained from human blood monocytes incubated with GM-CSF plus IL-4 (IL4-DC), GM-CSF plus IFNα (IFN-DC), or GM-CSF alone (GM-DC), with or without LPS maturation. PaCS developed as monomorphic aggregates of proteasome-reactive barrel-like particles only in ribosomes-rich cytoplasmic areas of differentiating IL4-DC. In contrast, DALIS formed as vesicular bodies storing K63-linked ubiquitinated proteins by coalescence of increased endosomal structures, in IFN-DC or after LPS maturation of GM-DC.

Correction: Dependence of the Ce(iii)/Ce(iv) ratio on intracellular localization in ceria nanoparticles internalized by human cells.

Correction for 'Dependence of the Ce(iii)/Ce(iv) ratio on intracellular localization in ceria nanoparticles internalized by human cells' by Daniela Ferraro, et al., Nanoscale, 2017, 9, 1527-1538.

Dependence of the Ce(iii)/Ce(iv) ratio on intracellular localization in ceria nanoparticles internalized by human cells.

CeO nanoparticles (CNPs) have been investigated as promising antioxidant agents with significant activity in the therapy of diseases involving free radicals or oxidative stress. However, the exact mechanism responsible for CNP activity has not been completely elucidated. In particular, in situ evidence of modification of the oxidative state of CNPs in human cells and their evolution during cell internalization and subsequent intracellular distribution has never been presented.

Overestimation of nanoparticles-induced DNA damage determined by the comet assay.

The increasing use of engineered nanoparticles (NPs) in a wide range of commercial products raises concern about the possible risks that NPs pose to human health. Many aspects of the interaction between living cells and NPs are still unclear, and a reliable assessment of NP genotoxicity would be important. One of the most common tests used for genotoxicity is the comet assay, a sensitive method measuring DNA damage in individual cells.

Particle-rich cytoplasmic structure (PaCS): identification, natural history, role in cell biology and pathology.

Cytoplasmic structures showing a selective concentration of both polyubiquitinated proteins and proteasome have been described in various epithelial, hematopoietic, mesenchymal and neural cells in vitro or in fetal tissues, as well as in chronically-infected, mutated preneoplastic and neoplastic tissues. These cytoplasmic structures differ from other ubiquitin-reactive cytoplasmic bodies, like sequestosomes, aggresome-like-induced structures in dendritic cells (DALIS)/non-dendritic cells (ALIS) and aggresomes in showing distinctive ultrastructural organization (particle-rich cytoplasmic structure or PaCS), a cytochemical pattern and a functional profile. Their formation can be induced in vitro in dendritic or natural killer cells by trophic factors and interleukin treatment.

Polyubiquitinated proteins, proteasome, and glycogen characterize the particle-rich cytoplasmic structure (PaCS) of neoplastic and fetal cells.

A particle-rich cytoplasmic structure (PaCS) concentrating ubiquitin-proteasome system (UPS) components and barrel-like particles in clear, cytoskeleton- and organelle-free areas has recently been described in some neoplasms and in genetic or infectious diseases at risk of neoplasia. Ultrastructurally similar particulate cytoplasmic structures, interpreted as glycogen deposits, have previously been reported in clear-cell neoplasms and some fetal tissues. It remains to be investigated whether the two structures are the same, colocalize UPS components and polysaccharides, and have a role in highly proliferative cells such as fetal and neoplastic cells.

PaCS is a novel cytoplasmic structure containing functional proteasome and inducible by cytokines/trophic factors.

A variety of ubiquitinated protein-containing cytoplasmic structures has been reported, from aggresomes to aggresome-like induced structures/sequestosomes or particle-rich cytoplasmic structures (PaCSs) that we recently observed in some human diseases. Nevertheless, the morphological and cytochemical patterns of the different structures remain largely unknown thus jeopardizing their univocal identification. Here, we show that PaCSs resulted from proteasome and polyubiquitinated protein accumulation into well-demarcated, membrane-free, cytoskeleton-poor areas enriched in glycogen and glycosaminoglycans.

Ubiquitin/proteasome-rich particulate cytoplasmic structures (PaCSs) in the platelets and megakaryocytes of ANKRD26-related thrombo-cytopenia.

ANKRD26-related thrombocytopenia (ANKRD26-RT) is an autosomal-dominant thrombocytopenia caused by mutations in the 5'UTR of the ANKRD26 gene. ANKRD26-RT is characterised by dysmegakaryopoiesis and an increased risk of leukaemia. PaCSs are novel particulate cytoplasmic structures with selective immunoreactivity for polyubiquitinated proteins and proteasome that have been detected in a number of solid cancers, in the epithelia of Helicobacter pylori gastritis and related preneoplastic lesions, and in the neutrophils of Schwachman-Diamond syndrome, a genetic disease with neutropenia and increased leukaemia risk.

Ubiquitin-proteasome-rich cytoplasmic structures in neutrophils of patients with Shwachman-Diamond syndrome.

Background: Shwachman-Diamond syndrome is an autosomal recessive disorder in which severe bone marrow dysfunction causes neutropenia and an increased risk of leukemia. Recently, novel particulate cytoplasmic structures, rich in ubiquitinated and proteasomal proteins, have been detected in epithelial cells and neutrophils from patients with Helicobacter pylori gastritis and several epithelial neoplasms.

Design And Methods: Blood neutrophils from 13 cases of Shwachman-Diamond syndrome - ten with and three without SBDS gene mutation - and ten controls were investigated by confocal microscopy and ultrastructural immunocytochemistry using antibodies against ubiquitinated proteins, proteasomes, p62 protein, and Helicobacter pylori VacA, urease and outer membrane proteins.

Proteasome particle-rich structures are widely present in human epithelial neoplasms: correlative light, confocal and electron microscopy study.

A novel cytoplasmic structure has been recently characterized by confocal and electron microscopy in H. pylori-infected human gastric epithelium, as an accumulation of barrel-like proteasome reactive particles colocalized with polyubiquitinated proteins, H. pylori toxins and the NOD1 receptor.

Actomyosin-dependent cortical dynamics contributes to the prophase force-balance in the early Drosophila embryo.

Background: The assembly of the Drosophila embryo mitotic spindle during prophase depends upon a balance of outward forces generated by cortical dynein and inward forces generated by kinesin-14 and nuclear elasticity. Myosin II is known to contribute to the dynamics of the cell cortex but how this influences the prophase force-balance is unclear.

Principal Findings: Here we investigated this question by injecting the myosin II inhibitor, Y27632, into early Drosophila embryos.

Cell-cycle inhibition by Helicobacter pylori L-asparaginase.

Helicobacter pylori (H. pylori) is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues.

A mitotic kinesin-6, Pav-KLP, mediates interdependent cortical reorganization and spindle dynamics in Drosophila embryos.

We investigated the role of Pav-KLP, a kinesin-6, in the coordination of spindle and cortical dynamics during mitosis in Drosophila embryos. In vitro, Pav-KLP behaves as a dimer. In vivo, it localizes to mitotic spindles and furrows.

In vivo accumulation of Helicobacter pylori products, NOD1, ubiquitinated proteins and proteasome in a novel cytoplasmic structure.

Cell internalization and intracellular fate of H. pylori products/virulence factors in vivo by human gastric epithelium, the main target of H. pylori-induced pathologies (i.