Erosion-Driven Enamel Crystallite Growth Phenomenon at the Tooth Surface In Vitro.

The erosion of tooth enamel is a common oral disease. The erosion pattern and location and the effects of nanoscale chemical composition on the erosion susceptibility of enamel have been well documented. However, the enamel remineralization accompanied by erosion and its underlying physicochemical mechanisms still remain poorly understood. Here, using rat molars selected for its good relevancy to human teeth, we investigated the remineralization behavior of the outermost enamel surface at the nanoscale level during erosion in diluted hydrochloric acid solutions. While particles on the outermost enamel surface that represent the termination of crystallites protruding to the surface from the near-surface core eroded by acid-attack, the lateral-growth of the particles (i.e., the main remineralization picture of the surface enamel) occurred concurrently. Ionic analyses indicate that the particle growth is driven by the local increase in pH near the eroding enamel surface as a result of the combination of the PO43- and CO32- released from the enamel surface with H+. As the pH increases eventually to the equilibrium pH level (∼5.5), a local supersaturation of solute ions is induced, resulting in particle growth. A simple growth model based on the experimental results together with an assumption that the particle growth is a diffusional process suggests that the particle growth rate is controlled by the degree of supersaturation and accommodation site for solute ions, which are affected by the pH of solution eroding the enamel surface. The remineralization mechanism presented by our study can explain how the enamel on being acid-exposed or tooth decay progress by beverage or food can naturally remineralize in the oral cavity and how remineralization can foster different surface topology at the nanoscale, depending on the pH value of etchant before the dental filling material is applied.

Dynamics of Ionic Liquids in Confinement by Means of NMR Relaxometry-EMIM-FSI in a Silica Matrix as an Example.

1H and 19F spin-lattice relaxation studies for 1-ethyl-3-methylimidazolium bis(fluorosulfonyl)imide in bulk and mesoporous MCM-41 silica matrix confinement were performed under varying temperatures in a broad range of magnetic fields, corresponding to 1H resonance frequency from 5Hz to 30MHz.A thorough analysis of the relaxation data revealed a three-dimensional translation diffusion of the ions in the bulk liquid and two-dimensional diffusion in the vicinity of the confining walls in the confinement. Parameters describing the translation dynamics were determined and compared. The rotational motion of both kinds of ions in the confinement was described by two correlation times that might be attributed to anisotropic reorientation of these species.

Genotoxic Potential Assessment of the Herbicide Bispyribac-Sodium in a Fresh Water Fish Clarias batrachus (Linn.).

Genotoxic potential of herbicide bispyribac-sodium was evaluated in fish Clarias batrachus using micronucleus (MN) test and comet assay. Fish were exposed to three environmentally relevant test concentrations of the herbicide for 20, 25 and 30 days. Significant effects (p < 0.05) for both concentration and duration of exposure were observed in herbicide exposed fish. Similar trend of DNA damage was observed through MN test and comet assay. Maximum DNA damage was observed in fish exposed to highest concentration of herbicide at all duration. Maximum damage was observed on day 25 at all concentrations followed by a decline. This study established C. batrachus as an ecotoxicological model for bispyribac-sodium induced genotoxicity testing. It further confirmed that both MN test and comet assay are useful tool for assessment of genotoxicity induced by water pollutants.

Influence of Lanthanum Doping on Structural and Electrical/Electrochemical Properties of Double Perovskite Sr2CoMoO6 as Anode Materials for Intermediate-Temperature Solid Oxide Fuel Cells.

Lanthanum (La3+)-doped double perovskites Sr2CoMoO6 (Sr2-xLaxCoMoO6, 0.00 ≤ x ≤ 0.03) were synthesized via the citrate-nitrate autocombustion route. The Reitveld refinement analysis of X-ray diffraction reveals the tetragonal symmetry as the main phase with space group I4/m and also confirms the presence of some peaks corresponding to extra phase SrMoO4. The SEM micrograph images reflect that grains are in irregular shape and sizes for all samples. Average grain size gradually decreases with the increase of the SrMoO4 phase. The X-ray photoelectron spectroscopy (XPS) analysis confirms the presence of mixed valence states of Mo5+/Mo6+, Co2+/Co3+, and O-lattice/O-chemisorbed/O-physisorbed species. Coefficient of thermal expansion (CTE) analysis shows that the particular composition Sr1.97La0.03CoMoO6 has the lowest CTE value among the compositions studied. The electrical conductivity of Sr2CoMoO6 is enhanced effectively by doping La at Sr sites. The measured area-specific resistance (ASR) for the composition Sr1.97La0.03CoMoO6 (SLCM03) is found to be appreciably low, ∼0.053 Ohm cm-2 at 800 °C. The obtained highest electrical conductivity with the lowest activation energy and low ASR value for the composition Sr1.97La0.03CoMoO6 encompasses it as a promising candidate for anode material in the intermediate-temperature solid oxide fuel cell (IT-SOFC) application.

Dynamical properties of EMIM-SCN confined in a SiO2 matrix by means of 1H NMR relaxometry.

1H nuclear magnetic resonance relaxometry is applied to investigate the translational and rotational dynamics of ionogels composed of an ionic liquid (IL): 1-ethyl-3-methyl-imidazolium-thiocyanate (EMIM-SCN) confined in a nanoporous SiO2 matrix. The relaxation studies were performed in the frequency range of 4 kHz-40 MHz and the temperature range of 223-248 K for different concentrations of the IL; the ratio (no. of moles of IL/no. of moles of SiO2) yields: 1/2, 3/5 and 7/10. A thorough analysis of this large set of experimental data was performed assuming the existence of two fractions of the liquid: a core fraction (near the pore center) and a surface fraction (near the confining walls). It was shown for all concentrations that the confinement does not significantly affect the translational motion near the pore center compared to the dynamics in bulk. The diffusion coefficients in the surface fraction are considerably smaller compared to the core fraction (from one to two orders of magnitude) and the difference becomes larger with increasing temperature. The diffusion coefficients become smaller for higher concentrations - this effect is not large, but visible. Very importantly, it was shown that, despite the interactions with the surface, the diffusion in the surface fraction remains of 3D character. As far as rotational dynamics in the surface fraction is concerned, it slows down compared to the bulk (and the core fraction), but this effect is of the order of factor 2-3.

Ninety days repeated dose oral toxicity study of Makaradhwaja in Wistar rats.

CONTEXT: Makaradhwaja is a KupipakwaRasayana. Since it contains two heavy metals, namely mercury and gold, it is essential to evaluate its safety. Hence, the present study was undertaken with an objective to evaluate toxicity and target organ of toxicity of Makaradhwaja if so. AIMS: The objective was to evaluate toxicological profile, the target organ of toxicity and to find no observed effect level (NOEL) or no observed adverse effect level (NOAEL) in rats after oral administration for ninety consecutive days. MATERIALS AND METHODS: Makaradhawaja preparation was administered to male and female Wistar rats for ninety consecutive days at 2.7, 13.5, and 27 mg/kg body weight. All relevant biochemical and hematological changes were observed. At termination, all the rats were sacrificed and necropsy was performed. Histopathological evaluation was also performed. STATISTICAL ANALYSIS USED: Dunnett's test followed by analysis of variance. RESULTS: There was a significant increase in high-dose group kidney weight of both sexes which could not be correlated with histopathology findings and serum biochemistry. Therefore, the change was not considered as an adverse effect. CONCLUSIONS: The dose level 27 mg/kg of Makaradhwaja was found as NOAEL and dose level 13.5 mg/kg of Makaradhwaja was found as NOEL.

Dynamics of ionic liquids in bulk and in confinement by means of (1)H NMR relaxometry - BMIM-OcSO4 in an SiO2 matrix as an example.

(1)H nuclear magnetic resonance relaxometry is applied to reveal information on the translational and rotational dynamics of the ionic liquid: 1-butyl-3-methyl imidazoliumoctyl sulfate (BMIM-OcSO4) in bulk and in a confinement formed by a nanoporous SiO2 matrix. The experimental studies were performed in a very broad frequency range, from 8 kHz to 40 MHz (referring to the (1)H resonance frequency), in order to probe motional processes at very different time scales using a single experiment, and in the temperature range of 243-303 K. The relaxation results for BMIM-OcSO4 in bulk are interpreted in terms of three relaxation contributions: a term associated with the translational dynamics of the ions (it has been assumed that the translational dynamics of cations and anions can be described by one diffusion coefficient) and two terms associated with the rotational motion of the anion and the cation, respectively. The relationships between the obtained dynamic parameters (rotational correlation times and translational diffusion coefficients) are thoroughly discussed and used as a "reference" for the dynamics of BMIM-OcSO4 confined in an SiO2 matrix. Analysis of the corresponding relaxation data for the confined liquid shows that the confinement does not significantly affect the rotational dynamics, but it has a considerable impact on the translational motion. It is demonstrated that the relaxation term associated with the translational dynamics stems from two contributions: a contribution from a core (bulk-like) fraction of the liquid and from a fraction moving near the pore surface and therefore being for some time adsorbed on the pore walls. The translational diffusion coefficient for the last fraction is determined and several conclusions regarding the residence lifetime of the ions on the surface are drawn. Moreover, an additional motional process on the timescale of ns or shorter is revealed in the confinement.

ß-Arrestin-2 Counters CXCR7-Mediated EGFR Transactivation and Proliferation.

UNLABELLED: The atypical 7-transmembrane chemokine receptor, CXCR7, transactivates the EGFR leading to increased tumor growth in several tumor types. However, the molecular mechanism of CXCR7 ligand-independent EGFR transactivation is unknown. We used cDNA knock-in, RNAi and analysis of mitogenic signaling components in both normal prostate epithelial cells and prostate cancer cells to decipher the proliferation-inducing mechanism of the CXCR7-EGFR interaction. The data demonstrate that CXCR7-induced EGFR transactivation is independent of both the release of cryptic EGFR ligands (e.g., AREG/amphiregulin) and G-protein-coupled receptor signaling. An alternate signaling mechanism involving ß-arrestin-2 (ARRB2/ß-AR2) was examined by manipulating the levels of ß-AR2 and analyzing changes in LNCaP cell growth and phosphorylation of EGFR, ERK1/2, Src, and Akt. Depletion of ß-AR2 in LNCaP cells increased proliferation/colony formation and significantly increased activation of Src, phosphorylation of EGFR at Tyr-1110, and phosphorylation/activation of ERK1/2 compared with that with control shRNA. Moreover, ß-AR2 depletion downregulated the proliferation suppressor p21. Stimulation of ß-AR2-expressing cells with EGF resulted in rapid nuclear translocation of phosphorylated/activated EGFR. Downregulation of ß-AR2 enhanced this nuclear translocation. These results demonstrate that ß-AR2 is a negative regulator of CXCR7/Src/EGFR-mediated mitogenic signaling. IMPLICATIONS: This study reveals that ß-AR2 functions as a tumor suppressor, underscoring its clinical importance in regulating CXCR7/EGFR-mediated tumor cell proliferation. Mol Cancer Res; 14(5); 493-503. ©2016 AACR.

Preparation of Self-Activated Fluorescence Mesoporous Silica Hollow Nanoellipsoids for Theranostics.

The newly developed multifunctional (self-activated fluorescent, mesoporous, and biocompatible) hollow mesoporous silica nanoellipsoids (f-hMS) are potentially useful as a delivery system of drugs for therapeutics and imaging purposes. For the synthesis of f-hMS, self-activated fluorescence hydroxyapatite (fHA) was used as a core template. A mesoporous silica shell was obtained by silica formation and subsequent removal of the fHA core, which resulted in a hollow-cored f-hMS. Although the silica shell provided a highly mesoporous structure, enabling an effective loading of drug molecules, the fluorescent property of fHA was also well-preserved in the f-hMS. Cytochrome c and doxorubicin, used as a model protein and anticancer drug, respectively, were shown to be effectively loaded onto f-hMS and were then released in a sustainable and controllable manner. The f-hMS was effectively taken up by the cells and exhibited fluorescent labeling while preserving excellent cell viability. Overall, the f-hMS nanoreservoir may be useful as a multifunctional carrier system for drug delivery and cell imaging.

Right-sided aortic arch with Kommerell's aneurysm.

We present a case report of a 55-year-old lady who presented with progressive dysphagia and was diagnosed with a Kommerell's aneurysm and a right-sided aortic arch. This case report outlines our management strategy and the challenges encountered during the perioperative period in a patient with this rare anomaly.

Low density ionogels obtained by rapid gellification of tetraethyl orthosilane assisted by ionic liquids.

A non-hydrolytic one pot sol-gel method has been used to synthesize mesoporous silica ionogels with the confined ionic liquid (IL) 1-ethyl 3-methyl imidazolium tetra fluoro-borate [EMIM][BF(4)]. The precursor for obtaining the SiO(2) matrix was tetraethyl orthosilicate (TEOS) and formic acid was used as a catalyst. These ionogels have been characterized by density measurements, TEM, BET, DSC, TGA and FTIR. The incorporation of the ionic liquid [EMIM][BF(4)] enhances the gellification rate which results in the ionogels having very low density (~0.3 g cm(-3)). The low density has been explained on the basis of the creation of 'blind embedded pores' in the matrix (apart from open pores) due to very rapid gellification (~1 min). Morphological studies provide experimental evidence for the presence of blind pores/voids inside the ionogel ingots. We have also shown that the IL entrapped in nanopores (~7-8 nm pore size) of the SiO(2) matrix has different physical properties than the bulk IL viz. (a) the phase transition temperatures (T(g), T(c) and T(m)) of the IL change upon confinement, (b) the thermal stability reduces upon confinement, and (c) the pore wall interaction with the IL results in changes in the C-H vibrations of the imidazolium ring and alkyl chain (the former increasing) which is also indicated in our DFT-calculation.

Toxicological evaluation of Panchakola Avaleha, an Ayurvedic classical formulation, in albino rats.

The present study was carried out to assess the safety of standardized Panchakola Avaleha on albino rats (Wistar strain). Animals were administered three doses of Panchakola Avaleha by oral routes, viz. higher (500 mg/kg/day), middle (250 mg/kg/day), and therapeutic dose (50 mg/ kg/ day) for 28 consecutive days. Effects of the test drug on hematological, biochemical, and histopathologic parameters were evaluated. This study revealed normal behavior, no mortality, and no significant changes in hematological, biochemical, and histopathological examinations.

Studies on imidazolium-based ionic liquids having a large anion confined in a nanoporous silica gel matrix.

The properties of large molecules confined in nanopores are expected to be different from those of the bulk. This study reports changes in the phase behavior and vibrational frequencies of an imidazolium-based ionic liquid (IL), namely, 1-butyl-3-methyl imidazolium octyl sulfate ([BMIM][OcSO(4)]) in a nanoporous silica gel matrix. Nanoporous silica gel matrixes have been synthesized by a one-step sol-gel technique using tetraethylorthosilicate (TEOS) as a starting precursor. The synthesized gel has been characterized by differential scanning calorimetry (DSC), BET, TEM and FTIR. The FTIR spectra show shifts in many vibrational bands; particularly, the vibrational bands related to the imidazolium ring, aliphatic chain, and SO(3) of the IL are found to shift significantly upon confinement. The DSC results show significant changes in the melting point (ΔT(m) ≈ 52 °C), crystallization temperature (ΔT(C) ≈ 14 °C), and glass transition temperature (ΔT(g) ≈ 2 °C). The IL used in the present study has a large anion ([OcSO(4)]), and ΔT(m) for this is much larger than those reported earlier for many other ILs with relatively smaller anions. A new approach, based on the liquid-drop model, has been suggested to explain this.

The IL-8-regulated chemokine receptor CXCR7 stimulates EGFR signaling to promote prostate cancer growth.

The proinflammatory chemokine receptor CXCR7 that binds the ligands CXCL11 and CXCL12 (SDF-1a) is elevated in a variety of human cancers, but its functions are not understood as it does not elicit classical chemokine receptor signaling. Here we report that the procancerous cytokine IL-8 (interleukin-8) upregulates CXCR7 expression along with ligand-independent functions of CXCR7 that promote the growth and proliferation of human prostate cancer cells (CaP cells). In cell culture, ectopic expression or addition of IL-8 selectively increased expression of CXCR7 at the level of mRNA and protein production. Conversely, suppressing IL-8 signaling abolished the ability of IL-8 to upregulate CXCR7. RNAi-mediated knockdown of CXCR7 in CaP cells caused multiple antitumor effects, including decreased cell proliferation, cell-cycle arrest in G(1) phase, and decreased expression of proteins involved in G(1) to S phase progression. In contrast, addition of the CXCR7 ligand SDF-1a and CXCL11 to CaP cells did not affect cell proliferation. Over expression of CXCR7 in normal prostate cells increased their proliferation in a manner associated with increased levels of phospho-EGFR (epidermal growth factor receptor; pY1110) and phospho-ERK1/2. Notably, coimmunoprecipitation studies established a physical association of CXCR7 with EGFR, linking CXCR7-mediated cell proliferation to EGFR activation. Consistent with these findings, CXCR7-depleted CaP tumors grew more slowly than control tumors, expressing decreased tumor-associated expression of VEGF, cyclin D1, and p-EGFR. Together, these results reveal a novel mechanism of ligand-independent growth promotion by CXCR7 and its coregulation by the proinflammatory factor IL-8 in prostate cancer.

Properties of ionic liquid confined in porous silica matrix.

Porous silica matrices of different pore sizes with confined ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate) [BMIM] [PF(6)] were prepared by sol-gel technique using a tetraethyl orthosilicate (TEOS) precursor with an aim to study the changes in physico-chemical properties of ionic liquid on confinement. It is found that on confinement 1) melting point decreases, 2) fluorescence spectra shows a red shift and 3) the vibrational bands are affected particularly those of imadazolium ring, which interacts more with the walls of the silica matrix. Preliminary theoretical calculations suggest that SiO(2) matrix interact more with the heterocyclic group of [BMIM] cation than the tail alkyl chain end group resulting in significant changes in the aromatic vibrations.

An MHC-I cytoplasmic domain/HIV-1 Nef fusion protein binds directly to the mu subunit of the AP-1 endosomal coat complex.

BACKGROUND: The down-regulation of the major histocompatibility complex class I (MHC-I) from the surface of infected cells by the Nef proteins of primate immunodeficiency viruses likely contributes to pathogenesis by providing evasion of cell-mediated immunity. HIV-1 Nef-induced down-regulation involves endosomal trafficking and a cooperative interaction between the cytoplasmic domain (CD) of MHC-I, Nef, and the clathrin adaptor protein complex-1 (AP-1). The CD of MHC-I contains a key tyrosine within the sequence YSQA that is required for down-regulation by Nef, but this sequence does not conform to the canonical AP-binding tyrosine-based motif Yxxphi, which mediates binding to the medium (micro) subunits of AP complexes. We previously proposed that Nef allows the MHC-I CD to bind the mu subunit of AP-1 (micro1) as if it contained a Yxxphimotif. METHODS AND FINDINGS: Here, we show that a direct interaction between the MHC-I CD/Nef and micro1 plays a primary role in the down-regulation of MHC-I: GST pulldown assays using recombinant proteins indicated that most of the MHC-I CD and Nef residues that are required for the down-regulation in human cells contribute to direct interactions with a truncated version of micro1. Specifically, the tyrosine residue of the YSQA sequence in the MHC-I CD as well as Nef residues E62-65 and P78 each contributed to the interaction between MHC-I CD/Nef and micro1 in vitro, whereas Nef M20 had little to no role. Conversely, residues F172/D174 and V392/L395 of the binding pocket on micro1 for Yxxphi motifs were required for a robust interaction. CONCLUSIONS: These data indicate that the MHC-I cytoplasmic domain, Nef, and the C-terminal two thirds of the mu subunit of AP-1 are sufficient to constitute a biologically relevant interaction. The data also reveal an unexpected role for a hydrophobic pocket in micro1 for interaction with MHC-I CD/Nef.

Evaluation of CaO-SiO2-P2O5-Na2O-Fe2O3 bioglass-ceramics for hyperthermia application.

Magnetic bioglass ceramics (MBC) are being considered for use as thermoseeds in hyperthermia treatment of cancer. While the bioactivity in MBCs is attributed to the formation of the bone minerals such as crystalline apatite, wollastonite, etc. in a physiological environment, the magnetic property arises from the magnetite [Fe3O4] present in these implant materials. A new set of bioglasses with compositions 41CaO x (52-x)SiO2 x 4P2O5 x xFe2O3 x 3Na2O (2 < or = x < or = 10 mol% Fe2O3) have been prepared by melt quenching method. The as-quenched glasses were then heat treated at 1050 degrees C for 3 h to obtain the glass-ceramics. The structure and microstructure of the samples were characterized using X-ray diffraction and microscopy techniques. X-ray diffraction data revealed the presence of magnetite in the heat treated samples with x > or = 2 mol% Fe2O3. Room temperature magnetic property of the heat treated samples was investigated using a Vibrating Sample Magnetometer. Field scans up to 20 kOe revealed that the glass ceramic samples had a high saturation magnetization and low coercivity. Room temperature hysteresis cycles were also recorded at 500 Oe to ascertain the magnetic properties at clinically amenable field strengths. The area under the magnetic hysteresis loop is a measure of the heat generated by the MBC. The coercivity of the samples is another important factor for hyperthermia applications. The area under the loop increases with an increase in Fe2O3 molar concentration and the. coercivity decreases with an increase in Fe2O3 molar concentration The evolution of magnetic properties in these MBCs as a function of Fe2O3 molar concentration is discussed and correlated with the amount of magnetite present in them.

Aspirin induces its anti-inflammatory effects through its specific binding to phospholipase A2: crystal structure of the complex formed between phospholipase A2 and aspirin at 1.9 angstroms resolution.

Phospholipase A2 is potentially an important target for structure-based rational drug design. In order to determine the involvement of phospholipase A2 in the action of non-steroidal anti-inflammatory drugs (NSAIDs), the crystal structure of the complex formed between phospholipase A2 and aspirin has been determined at 1.9 angstroms resolution. The structure contains 915 protein atoms, 1 calcium ion, 13 atoms of aspirin and 105 water molecules. The observed electron density of the aspirin molecule in the structure was of very high quality thus allowing the precise determination of its atomic coordinates leading to the clear description of its interactions with the enzyme. The structure of the complex clearly shows that aspirin is literally embedded in the hydrophobic environment of PLA2. It is so placed in the substrate binding channel that it forms several important attractive interactions with calcium ion, His 48 and Asp 49. Thus, the structure of the complex clearly shows that aspirin occupies a favourable place in the specific binding site of PLA2. The binding studies have shown that acetyl salicylate (aspirin) binds to PLA2 enzyme specifically with a dissociation constant of 6.4 x 10(-6) M. The structural details and binding data suggest that the inhibition of PLA2 by aspirin is of pharmacological

Design of specific peptide inhibitors for group I phospholipase A2: structure of a complex formed between phospholipase A2 from Naja naja sagittifera (group I) and a designed peptide inhibitor Val-Ala-Phe-Arg-Ser (VAFRS) at 1.9 A resolution reveals unique features.

Phospholipase A(2) (PLA(2)) (E. C. 3.1.1.4) is a common enzyme in the two-way cascade mechanism leading to the production of proinflammatory compounds known as eicosanoids. The binding of phospholipase A(2) to the membrane surface and hydrolysis of phospholipids are thought to involve the formation of a hydrophobic channel into which a single substrate molecule diffuses before its cleavage. To regulate the production of proinflammatory compounds, a specific peptide inhibitor Val-Ala-Phe-Arg-Ser (VAFRS) for the group I PLA(2) enzymes has been designed and synthesized. PLA(2) was isolated from Indian cobra (Naja naja sagittifera) venom and purified to homogeneity. The binding studies indicated the K(i) value of 1.02 +/- 0.10 x 10(-8) M. The purified PLA(2) samples and the designed inhibitor VAFRS were cocrystallized. The crystal structure of the complex was determined and refined to 1.9 A resolution. The peptide binds to PLA(2) at the active site and fills the hydrophobic channel completely. However, its placement with respect to the channel is in the opposite direction as compared to those observed in group II PLA(2)'s. Furthermore, the predominant intermolecular interactions involve strong electrostatic interactions between the side chains of peptide Arg and Asp 49 of PLA(2) together with a number of van der Waals interactions with other residues. A good number of observed interactions between the peptide and the protein indicate the significance of a structure-based drug design approach. The novel factor in the present sequence of the peptide is related to the introduction of a positively charged residue at the C-terminal part of the peptide.