Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model

Background  

Experimental studies provide evidence that inhaled nanoparticles may translocate over the airspace epithelium and cause increased cellular inflammation. Little is known, however, about the dependence of particle size or material on translocation characteristics, inflammatory response and intracellular localization.     

Comparative Analysis of Single-Molecule Dynamics of TRPV1 and TRPV4 Channels in Living Cells

TRPV1 and TRPV4, members of the transient receptor potential vanilloid family, are multimodal ion channels activated by various stimuli, including temperature and chemicals. It has been demonstrated that TRPV channels function as tetramers; however, the dynamics of the diffusion, oligomerization, and endocytosis of these channels in living cells are unclear. Here we undertook single-molecule time-lapse imaging of TRPV1 and TRPV4 in HEK 293 cells. Differences were observed between TRPV1 and TRPV4 before and after agonist stimulation. In the resting state, TRPV4 was more likely to form higher-order oligomers within immobile membrane domains than TRPV1. TRPV1 became immobile after capsaicin stimulation, followed by its gradual endocytosis. In contrast, TRPV4 was rapidly internalized upon stimulation with GSK1016790A. The selective loss of immobile higher-order oligomers from the cell surface through endocytosis increased the proportion of the fast-diffusing state for both subtypes. With the increase in the fast state, the association rate constants of TRPV1 and TRPV4 increased, regenerating the higher-order oligomers. Our results provide a possible mechanism for the different rates of endocytosis of TRPV1 and TRPV4 based on the spatial organization of the higher-order structures of the two TRPV channels.     

Preparation and characterization of CuO nanoparticles encapsulated in mesoporous Silica

CuO nanoparticles supported in mesoporous silica MCM-41 (or CuO-nano-MCM-41 nanocomposites) were prepared via an in situ method. A 2.10 wt.% Cu loading was achieved without the loss of pore ordering. Highly dispersed and uniform CuO nanoparticles could be detected using transmission electron microscopy (TEM) confirming also the absence of large particles outside the mesopore silica. The bandgaps of the resulting CuO particles are widened from 1.7 to 3.15 eV for an indirect allowed bandgap and from 3.25 to 4.43 eV for a direct allowed interband transition owing to the quantum size effect.     

Size-partitioning of an urban aerosol to identify particle determinants involved in the proinflammatory response induced in airway epithelial cells

Background  

The contribution of air particles in human cardio-respiratory diseases has been enlightened by several epidemiological studies. However the respective involvement of coarse, fine and ultrafine particles in health effects is still unclear. The aim of the present study is to determine which size fraction from a chemically characterized background aerosol has the most important short term biological effect and to decipher the determinants of such a behaviour.     

Silica nanoparticles self-assembly process in polymer composites: Towards advanced materials

The incorporation of silica nanoparticles (Si-NPs) into the polymer matrix is a growing area of interest research to produce high-performance polymer nanocomposites (NCs) across a wide range of nanotechnology applications. This improvement is due to the Si-NPs capability to self-assembly giving rise to specific well-organized structures with both short- and long-range order across a hierarchy of spatial scales, determined by both NP-NP and NP-matrix interactions, involving a careful balance among attractive driving forces, repulsive forces, and directional forces.Respect to this, the aim of the present paper is to systematically review the use of Si-NPs in polymer NCs and on the role of NPs self-assembly in determining the final material properties.Firstly, we explored the synthesis and modification of both isotropic and anisotropic Si-NPs in relation with use in NC materials, focusing on NPs dispersion and distribution, as well as on the functionalization strategies of Si-NPs. Besides Si-NPs functionalization with conventional small organic molecules, a large section is devoted to an emerging class of functionalized Si-NPs with macromolecules, namely silica hairy NPs (Si-HNPs), able to give rise a rich variety of complex assemblies and materials with new structures and functionalities. Successively, NCs materials containing Si-NPs and Si-HNPs have been explored in terms of synthetic preparation and properties. The self-organization of Si-NPs and Si-HNPs in polymer matrices has been reported and its effect on the functional materials properties have been evaluated with a critical point of view on the results, limits, and future perspectives.Our review can be considered a tutorial work, aiming at providing useful insights to researchers in the field of nanotechnology and nanoscience, taking into consideration the fundamental role of NPs self-assembly processes in determining the functional material properties.     

Carbon black nanoparticles induce type II epithelial cells to release chemotaxins for alveolar macrophages

Background  

Alveolar macrophages are a key cell in dealing with particles deposited in the lungs and in determining the subsequent response to that particle exposure. Nanoparticles are considered a potential threat to the lungs and the mechanism of pulmonary response to nanoparticles is currently under intense scrutiny. The type II alveolar epithelial cell has previously been shown to release chemoattractants which can recruit alveolar macrophages to sites of particle deposition. The aim of this study was to assess the responses of a type II epithelial cell line (L-2) to both fine and nanoparticle exposure in terms of secretion of chemotactic substances capable of inducing macrophage migration.     

Silica coating of Fe3O4 magnetic nanoparticles with PMIDA assistance to increase the surface area and enhance peptide immobilization efficiency

The high efficiency of using N-(phosphonomethyl)iminodiacetic acid (PMIDA) as a surfactant for formation of a silica coating on Fe₃O₄ magnetic nanoparticles (MNPs) with a large surface area has been demonstrated. The coating of PMIDA-stabilized MNPs with silica and their further APS-functionalization significantly increased the specific area (up to 203 m² g^?1) and the number of amino groups (up to 1.12 mmol/g) grafted on their surface compared to nanomaterials synthesized without preliminary SiO₂-coating. The comparative study of the peptide modification efficiency, using as an example pH-low insertion peptide (pHLIP), of MNPs coated with 3-aminopropylsilane (APS) or SiO₂/APS was carried out. It has been shown that silica coating of PMIDA-stabilized MNPs leads to a significant increase in the degree of immobilization of the peptide (up to 22 μmol per g of MNPs). Comprehensive characterization of the obtained materials at each stage of the synthesis was carried out using scanning electron microscopy (SEM), energy dispersive X-ray fluorescence spectroscopy (EDX), BET analysis, ATR Fourier transformed infrared spectroscopy (FTIR), termogravimetric analysis (TGA), CHN-elemental analysis, dynamic light scattering (DLS), and vibrating sample magnetometry (VSM). The proposed approach to applying SiO₂-coating of MNPs can be useful for design of new materials for biomedical and chemical purposes.     

Regulation of the Membrane Trafficking of the Mechanosensitive Ion Channels TRPV1 and TRPV4 by Zonular Tension,Osmotic Stress and Activators in the Mouse Lens

Lens water transport generates a hydrostatic pressure gradient that is regulated by a dual-feedback system that utilizes the mechanosensitive transient receptor potential vanilloid (TRPV) channels, TRPV1 and TRPV4, to sense changes in mechanical tension and extracellular osmolarity. Here, we investigate whether the modulation of TRPV1 or TRPV4 activity dynamically affects their membrane trafficking. Mouse lenses were incubated in either pilocarpine or tropicamide to alter zonular tension, exposed to osmotic stress, or the TRPV1 and TRPV4 activators capsaicin andGSK1016790A (GSK101), and the effect on the TRPV1 and TRPV4 membrane trafficking in peripheral fiber cells visualized using confocal microscopy. Decreases in zonular tension caused the removal of TRPV4 from the membrane of peripheral fiber cells. Hypotonic challenge had no effect on TRPV1, but increased the membrane localization of TRPV4. Hypertonic challenge caused the insertion of TRPV1 and the removal of TRPV4 from the membranes of peripheral fiber cells. Capsaicin caused an increase in TRPV4 membrane localization, but had no effect on TRPV1; while GSK101 decreased the membrane localization of TRPV4 and increased the membrane localization of TRPV1. These reciprocal changes in TRPV1/4 membrane localization are consistent with the channels acting as mechanosensitive transducers of a dual-feedback pathway that regulates lens water transport.     

Silica nanoparticles assisted preparation of reddish-yellow emitting Eu2+ activated remote-type CaSrSiO4 phosphor for warm white LED applications

A reddish-yellow emitting silicate-based remote phosphor has been developed via the wet-solid phase reaction technique. By employing silica nanoparticles (200 nm), Eu²⁺ doped CaSrSiO₄ phosphor was developed and its efficacy has been examined thoroughly. The developed remote phosphor can get excited over a broad region of the spectrum ranging from ultraviolet to blue (250–500 nm) and as generates a reddish-yellow emission peaked at 580 nm covering a broad range of spectral components (450–800 nm) with a quantum efficiency of 52%. The thermoluminescence studies of developed remote phosphor exhibit 50% of the stable emission up to 200 °C without any shift in the emission wavelength. The developed remote phosphor was then utilized for the making of a proto-type LED using 450 nm blue-emitting commercial LED. The output emission from the proto-type LED confirms the production of efficient warm white light with CCT <5000 K and CRI >85.     

Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells

TRPV4 (transient receptor potential vanilloid 4), a calcium permeable TRP ion channel, is known to play a key role in endocytosis. However, whether it contributes to exocytosis remains unclear. Here, we report that activation of TRPV4 induced massive exocytosis in both melanoma A375 cell and heterologous expression systems. We show here that, upon application of TRPV4-specific agonists, prominent vesicle priming from endoplasmic reticulum (ER) was observed, followed by morphological changes of mitochondrial crista may lead to cell ferroptosis. We further identified interactions between TRPV4 and folding/vesicle trafficking proteins, which were triggered by calcium entry through activated TRPV4. This interplay, in turn, enhanced TRPV4-mediated activation of folding and vesicle trafficking proteins to promote exocytosis. Our study revealed a signaling mechanism underlying stimulus-triggered exocytosis in melanoma and highlighted the role of cellular sensor TRPV4 ion channel in mediating ferroptosis.     

TRPV4 Promotes Metastasis in Melanoma by Regulating Cell Motility through Cytoskeletal Rearrangement

The abnormal expression of Transient Receptor Potential cation channel subfamily V member 4 (TRPV4) is closely related to the progression of multiple tumors. In addition, TRPV4 is increasingly being considered a potential target for cancer therapy, especially in tumor metastasis prevention. However, the biological correlation between TRPV4 and tumor metastasis, as well as the specific role of TRPV4 in malignant melanoma metastasis, is poorly understood. In this study, we aimed to examine the role of TRPV4 in melanoma metastasis through experiments and clinical data analysis, and the underlying anticancer mechanism of Baicalin, a natural compound, and its inhibitory effect on TRPV4 with in vivo and in vitro experiments. Our findings suggested that TRPV4 promotes metastasis in melanoma by regulating cell motility via rearranging the cytoskeletal, and Baicalin can inhibit cancer metastasis, whose mechanisms reverse the recruitment of activated cofilin to leading-edge protrusion and the increasing phosphorylation level of cortactin, which is provoked by TRPV4 activation.     

Axial dispersion in parallel channel electrochemical cells

Measurements have been made of axial dispersion in models of a parallel channel electrolyser and a magnesium/silver chloride seawater battery under laminar flow conditions.Experimental results have been interpreted with the aid of three theoretical models; while these have been shown to be less than perfect they reveal the highly structured nature of the flow in the absence of bubbles. When nitrogen is sparged into the system to simulate anodic or cathodic gas evolution the mixing regime changes drastically. The results obtained have been compared with observations made on various organosyntheses and the performance of a seawater battery.     

Silica nanoparticles induce neurodegeneration-like changes in behavior,neuropathology, and affect synapse through MAPK activation

Background

Silica nanoparticles (SiO₂-NPs) are naturally enriched and broadly utilized in the manufacturing industry. While previous studies have demonstrated toxicity in neuronal cell lines after SiO₂-NPs exposure, the role of SiO₂-NPs in neurodegeneration is largely unknown. Here, we evaluated the effects of SiO₂-NPs-exposure on behavior, neuropathology, and synapse in young adult mice and primary cortical neuron cultures.

Results

Male C57BL/6 N mice (3 months old) were exposed to either vehicle (sterile PBS) or fluorescein isothiocyanate (FITC)-tagged SiO₂-NPs (NP) using intranasal instillation. Behavioral tests were performed after 1 and 2 months of exposure. We observed decreased social activity at both time points as well as anxiety and cognitive impairment after 2 months in the NP-exposed mice. NP deposition was primarily detected in the medial prefrontal cortex and the hippocampus. Neurodegeneration-like pathological changes, including reduced Nissl staining, increased tau phosphorylation, and neuroinflammation, were also present in the brains of NP-exposed mice. Furthermore, we observed NP-induced impairment in exocytosis along with decreased synapsin I and increased synaptophysin expression in the synaptosome fractions isolated from the frontal cortex as well as primary neuronal cultures. Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were also activated in the frontal cortex of NP-exposed mice. Moreover, inhibition of ERK activation prevented NP-mediated changes in exocytosis in cultured neurons, highlighting a key role in the changes induced by NP exposure.

Conclusions

Intranasal instillation of SiO₂-NPs results in mood dysfunction and cognitive impairment in young adult mice and causes neurodegeneration-like pathology and synaptic changes via ERK activation.

     

Emerging Role of Transient Receptor Potential Vanilloid 4 (TRPV4) Ion Channel in Acute and Chronic Itch

Itch is a clinical problem that leaves many sufferers insufficiently treated, with over 20 million cases in the United States. This is due to incomplete understanding of its molecular, cellular, and cell-to-cell signaling mechanisms. Transient receptor potential (TRP) ion channels are involved in several sensory modalities including pain, vision, taste, olfaction, hearing, touch, and thermosensation, as well as itch. Relative to the extensive studies on TRPV1 and TRPA1 ion channels in itch modulation, TRPV4 has received relatively little research attention and its mechanisms have remained poorly understood until recently. TRPV4 is expressed in ganglion sensory neurons and a variety of skin cells. Growing evidence in the past few years strongly suggests that TRPV4 in these cells contributes to acute and chronic disease-associated itch. This review focuses on the current experimental evidence involving TRPV4 in itch under pathophysiological conditions and discusses its possible cellular and molecular mechanisms.     

Kupffer cells are central in the removal of nanoparticles from the organism

Background  

The study aims at revealing the fate of nanoparticles administered intravenously and intraperitoneally to adult female mice, some of which were pregnant. Gold nanoparticles were chosen as a model because these particles have been found to be chemically inert and at the same time are easily traced by autometallography (AMG) at both ultrastructural and light microscopic levels.     

Expression Profiles of ASIC1/2 and TRPV1/4 in Common Skin Tumors

The acid-sensing ion channels ASIC1 and ASIC2, as well as the transient receptor potential vanilloid channels TRPV1 and TRPV4, are proton-gated cation channels that can be activated by low extracellular pH (pH_e), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear. In this study, we investigated the expression profiles of ASIC1, ASIC2, TRPV1 and TRPV4 in malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and in nevus cell nevi (NCN). We conducted immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express ASIC1/2 and TRPV1/4. Striking results were that BCCs are often negative for ASIC2, while nearly all SCCs express this marker. Epidermal MM sometimes seem to lack ASIC1 in contrast to NCN. Dermal portions of MM show strong expression of TRPV1 more frequently than dermal NCN portions. Some NCN show a decreasing ASIC1/2 expression in deeper dermal tumor tissue, while MM seem to not lose ASIC1/2 in deeper dermal portions. ASIC1, ASIC2, TRPV1 and TRPV4 in skin tumors might be involved in tumor progression, thus being potential diagnostic and therapeutic targets.     

氮化硅对注凝成型熔融石英陶瓷性能影响的研究

以丙烯酰胺(AM)为有机单体,N,N'-亚甲基丙稀酰胺(MBAM)为交联剂,过硫酸铵(APS)为引发剂,pH=3.5,温度为1190 ℃保温5 h的条件下,采用注凝成型方法制备熔融石英陶瓷;以氮化硅为添加剂,通过XRD、SEM等分析不同氮化硅添加量对熔融石英陶瓷的影响,结果表明,氮化硅促进石英陶瓷的烧结,不会导致方石英出现;试样常温抗折强度、体积密度随氮化硅添加量的增加而增大,而显气孔率随氮化硅添加量的增加而减小.当氮化硅添加量为2%时,试样常温抗折强度为37.13 MPa,体积密度为1.96 g/cm3 ,显气孔率为10%.     

Magnetic resonance of the NiFe2O4 nanoparticles in the gigahertz range

We report an adjustable magnetic resonance frequency from 1.45 to 2.54 GHz for NiFe₂O₄ nanoparticles which were prepared by a sol–gel process. X-ray diffraction and scanning electron microscopy results indicate that the samples are polycrystalline nanoparticles, and the size of the particles increases obviously with the thermal treatment temperature. The consequence of the surface composition suggests that the oxygen defects are present in the nanoparticle surface, and this surface magnetic state can show a strong surface anisotropy. With decreasing size of the particle, the surface magnetic effect is predominant, resulting in an increase of resonance frequency for NiFe₂O₄ nanoparticles. This finding provides a new route for NiFe₂O₄ materials that can be used in the gigahertz range.     

Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

Background  

A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red) and analyzed 2 time points (3 and 24 hours) for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality) was calculated.