Redox Dyshomeostasis Strategy for Hypoxic Tumor Therapy Based on DNAzyme-Loaded Electrophilic ZIFs.

Redox homeostasis is one of the main reasons for reactive oxygen species (ROS) tolerance in hypoxic tumors, limiting ROS-mediated tumor therapy. Proposed herein is a redox dyshomeostasis (RDH) strategy based on a nanoplatform, FeCysPW@ZIF-82@CAT Dz, to disrupt redox homeostasis, and its application to improve ROS-mediated hypoxic tumor therapy. Once endocytosed by tumor cells, the catalase DNAzyme (CAT Dz) loaded zeolitic imidazole framework-82 (ZIF-82@CAT Dz) shell can be degraded into Zn2+ as cofactors for CAT Dz mediated CAT silencing and electrophilic ligands for glutathione (GSH) depletion under hypoxia, both of which lead to intracellular RDH and H2 O2 accumulation. These "disordered" cells show reduced resistance to ROS and are effectively killed by ferrous cysteine-phosphotungstate (FeCysPW) induced chemodynamic therapy (CDT). In vitro and in vivo data demonstrate that the pH/hypoxia/H2 O2 triple stimuli responsive nanocomposite can efficiently kill hypoxic tumors. Overall, the RDH strategy provides a new way of thinking about ROS-mediated treatment of hypoxic tumors.

[pH-dependent rearrangements in the influenza A virus].

The Influenza virus possesses two modules: internal ribonucleoprotein (RNP) containing the viral genome RNA and external lipid envelope with transmembrane ionic channel protein M2 and embedded glycoproteins hemagglutinin (HA) and neuraminidase (NA) forming surface spike ends. These modules are combined in a whole virion by the matrix protein M1. The effect of the acidic pH 4,2-4,5 on the influenza virus grown in MDCK-H cells was tested. The A/Aichi/68 (H3N2) virus synthesized in MDCK-H cells was shown to contain uncleaved HA0 (m.w. 78 kD) and provide low infectivity. This virus was resistant to acidic medium and non-permeable to the phosphotungsten acid (PTA) used in electron microscopy as a contrast stain, and did not reduce infectious potential after acidic treatment. The trypsin-activated virus containing cleaved HA1 (56 kD)+HA2 (22 kD) was sensitive to acidic exposition resulting in the appearance of permeability to PTA, reduction of infectivity, enhancement of the M1-RNP interlink. These data indicate that the structural form of the cleaved HA1 +HA2 surface hemagglutinin coordinates a transmembrane interaction between surface and internal virus components.

Computational and experimental elucidation of the boosted stability and antibacterial activity of ZIF-67 upon optimized encapsulation with polyoxometalates.

Water microbial purification is one of the hottest topics that threats human morbidity and mortality. It is indispensable to purify water using antimicrobial agents combined with several technologies and systems. Herein, we introduce a class of nanosized metal organic framework; Zeolitic imidazolate framework (ZIF-67) cages encapsulated with polyoxometalates synthesized via facile one-step co-precipitation method. We employed two types of polyoxometalates bioactive agents; phosphotungstic acid (PTA) and phosphomolybdic acid (PMA) that act as novel antibacterial purification agents. Several characterization techniques were utilized to investigate the morphological, structural, chemical, and physical properties such as FESEM, EDS, FTIR, XRD, and N2 adsorption/desorption isotherms techniques. The antibacterial assessment was evaluated using colony forming unit (CFU) against both Escherichia coli and Staphylococcus aureus as models of Gram-negative and Gram-positive bacteria, respectively. The PTA@ZIF-67 showed higher microbial inhibition against both Gram-positive and Gram-negative bacteria by 98.8% and 84.6%, respectively. Furthermore, computational modeling using density functional theory was conducted to evaluate the antibacterial efficacy of PTA when compared to PMA. The computational and experimental findings demonstrate that the fabricated POM@ZIF-67 materials exhibited outstanding bactericidal effect against both Gram-negative and Gram-positive bacteria and effectively purify contaminated water.

11-Tungstophosphate with iron(II) and hydrogen peroxide efficiently detached bacterial biofilm.

An attempt was made to detach bacterial biofilm, formed by Staphylococcus epidermidis, by using hydrogen peroxide (H(2)O(2)) and tungsten compounds. When iron(II) (Fe(2+)) was mixed with undecatungstophosphate ([PW(11)O(39)](7-)) and then H(2)O(2), the resulting mixture was able to totally remove the biofilm probably because of co-generation of (1)O(2) and .OH. A mixture of undecatungstosilicate ([SiW(11)O(39)](8-)) and Fe(2+) (or Cu(2+)) also gave a good result, but their catalytic activities for producing .OH (or (1)O(2)) were rather weak. An electron microscopic study showed that almost nothing was visible on the surface of a biofilm-coated glass after treatment with 1mM [PW(11)O(39)](7-)+1 mM Fe(2+) and 500 mM H(2)O(2) (incubated for 1 h at 37 degrees C).

Preparation of poly(MAA-g-EG) hydrogel nanoparticles by a thermally-initiated free radical dispersion polymerization.

Poly(methacrylic acid-grafted-poly(ethylene glycol)) (P(MAA-g-EG)) hydrogel nanoparticles (HNPs) were prepared by a thermally-initiated free radical dispersion polymerization method. The effects of various reaction parameters on the preparation of HNPs were investigated, including the quantity of monomer, temperature, initiator dosage, crosslinker dosage, and co-stabilizer concentration. The reaction temperature at 75 degrees C was found to be suitable for preparing stable and small P(MAA-g-EG) HNPs. By adding a little amount of polyvinyl alcohol in the reaction media, P(MAA-g-EG) HNPs with narrow size distribution could be obtained. The effects of pH and the crosslinker dosage on the equilibrium swelling behavior of P(MAA-g-EG) HNPs were also studied. The P(MAA-g-EG) HNPs perform pH-responsive swelling behavior, which is strongly influenced by the crosslinker dosage.

[Detection of the sensitivity of some bacteria and fungi to the action of sodium phosphotungstate beta-Na6[P2W18O62].18 H2O]. / Determinarea sensibilitatii unor bacterii si ciuperci la actiunea fosfowolframatului de sodiu beta-Na6[P2W18O62].18 H2O.

Poliyoxometalales are a very special category of the chemical compounds that have multiply properties and possibility to application in a lot of actual domain of the scientific research. One of the most practice application of the polyoxometalates with a special significance is their antibacterial and anti fungus actions. For this study, there have been used fungus, Gram-positive and Gram-negative bacteria, and the action of the polyoxometalates was tested simultaneously with the action of the specifically antibiotics for the studied bacteria. In order to determine the fungus and bacteria sensibility to the tested substance, there have been used three methods: two qualitative, diffusion methods (rondel and bucket methods) and one quantitative method (determination of the minimum inhibitory concentration-MIC). The results of the bucket method were similarly with ones obtained with the rondel method: only Staphylococcus aureus strains were sensitive to the sodium phosphotungstate. Using the quantitative method (MIC) have been emphasized that Pseudomonas aeruginosa and Klebsiella pneumoniae strains were sensitive in time to the studied substance.

The enhancing effects of anion channel blockers on sperm activation by bicarbonate.

We found that anion channel blockers such as phosphotungstate and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) enhanced HCO3(-)-induced activation on porcine epididymal sperm. In the presence of these compounds, HCO3- increased the motility, respiration rate and especially the cAMP content of the sperm to a greater extent than did HCO3- alone. The enhancing effects were not observed in the absence of HCO3-, but were evident when the concentration of HCO3- was low. These compounds did not significantly alter the intracellular pH and did inhibit the adenylate cyclase activity of the sperm plasma membrane. When these compounds were added to sperm homogenate with ATP, the cAMP formed was reduced compared to the control. In addition, these compounds inhibited both the SO4(2-) influx and efflux of the sperm. From these results, we conclude that the anion channel blockers tested principally inhibit the efflux of endogenous HCO3- derived from metabolic CO2, so that HCO3- accumulates intracellularly and stimulates the adenylate cyclase of the sperm.

[The morphology of the micro-capsulated polyacrylic acid-based formulation of measles vaccine].

The morphology and virus localization were studied in the microcapsulated measles vaccine formulation involving polyacrylic acid (PAA) copolymers as a matrix. Transmission electron microscopy and phosphotungsic staining at a pH value of 2 to 7 showed that the morphology of microparticles was related to the value of pH and to the concentration of a polymer in the matrix. In the neutral medium, the microcapsules had the sizes of 0.5 to 10 microm, which were optimal for transport through the intestinal wall when immunization was orally used. Immunocytochemistry revealed measles virus antigen within the microparticles. The specific activity of the microcapsulated formulation of measles virus was as high as 3.36 and 4.31 lg of TCD50/0.5 ml for the samples containing 1 and 0.1% polymer, respectively. The findings suggest that the microparticles of the vaccine contain live measles virus.

Phosphotungstate shows a heparin-like anticoagulant effect but inhibits heparin.

We examined the anticoagulant effects of phosphotungstate (PTA). PTA inhibited factors IIa and Xa activity only in the presence of antithrombin III (ATIII). The inhibitory effect of PTA on IIa was much smaller than that on Xa. When PTA was added to heparin (Hep), the inhibitory effect of Hep on IIa was reduced. As a result of charge interaction, PTA showed an inhibitory effect on anion transport activity of the erythrocyte, a potent salting-in effect and a metachromatic reaction on toluidine blue (TolB). Silicotungstate (STA) showed almost the same results as PTA. These effects of PTA and STA were not replaced by their constituents, tungstate, silicate and phosphate, but may arise from their high anionic valency.

Failure to demonstrate a protein coat on enamel crystallites by morphological means.

Phosphotungstic acid (PTA) treatment of section of Epon-embedded enamel dissolves the crystallites and stains material postulated to be crystal-bound proteins. Alternative, capillarity forces within the channels left after crystallite removal may draw in PTA. This prediction was tested on three systems. (1) Protein free synthetic hydroxyapatite was embedded in Epon; treatment of thin sections with PTA removed most crystals, leaving empty holes outlined by stain that could not represent protein. (2) Sections of rat incisor enamel were treated with PTA and then re-embedded in Epon and sectioned at 90 degrees to the original plane. In these sections-of-section the cut ends of dissolved crystallite profiles were coated with stain. To determine if stained protein coats can be detected in the absence of the crystallite profiles, Epon sections were partially demineralized with formic acid, re-embedded in Epon and sections-of section were PTA treated. Previously extracted crystallites left no stained coats, and only the crystallites that were not removed by formic acid left PTA-stained outlines. (3) PTA-treated sections of dogfish shark enameloid were flooded with 5-nm colloidal gold particles and sections-of-section were prepared. The presence of gold particles on the section surface and in holes previously occupied by crystallites suggested that PTA solution could also be sucked into similar holes. It is concluded that PTA outlines are not crystal-bound proteins but artefacts caused by stain lining holes left in the section when the crystallites have been extracted.

Differential reactivity of structural components of eosinophil leucocyte granules as revealed by ethanolic phosphotungstic acid.

After glutaraldehyde fixation and ethanolic phosphotungstic acid (E-PTA) treatment before embedding, thin sections of rat bone marrow and large intestine showed a characteristic pattern of electron opacity in eosinophil leucocyte granules. In both mature eosinophils and precursor cells, the matrix appeared highly contrasted while the crystalline core revealed no electron density. Additional treatment of sections with uranyl acetate did not modify the contrasting pattern of eosinophil granules. The absence of electron dense reaction in the crystalline core after E-PTA treatment seems to originate from removal of core components. The selective reactivity of the matrix toward E-PTA could be a valuable ultrastructural marker for studies on the differentiation of specific granules along the maturation of eosinophil leucocytes.

Electron microscopic contrast of the cytoskeleton and junctional complexes of intestinal epithelial cells by ethanolic phosphotungstic acid.

After glutaraldehyde fixation and treatment with ethanolic phosphotungstic acid (E-PTA) before plastic embedding, sections of rat large intestine showed a characteristic electron contrasting pattern in epithelial cells. The axis of microvilli, terminal web, a thin band below the luminal plasma membrane, centrioles and junctional complexes (tight junctions, adherens junctions, and desmosomes) appeared highly contrasted. In addition to protein components of microfilaments and intermediate filaments, proteins from the junctional complexes could also be implicated in the contrasting reaction with E-PTA. Mitochondrial membranes, chromatin masses, and nucleoli of enterocytes showed considerable electron density, whereas no reaction was found in the glycocalyx and mucin content of goblet cells. The clear visualization of cytoskeleton elements and junctional complexes by E-PTA contrasting represents a simple and valuable method for studies on the normal and pathological organization of these structures in epithelial cells.

[Effect of the contrast conditions using solutions of phosphotungstic acid on the electron microscopic image of the foot-and-mouth disease virus]. / Vliianie uslovii kontrastirovaniia rastvorami fosfornovol'framovoi kisloty na élektronno-mikroskopicheskoe izobrazhenie virusa iashchura.

A method of negative staining of foot-and-mouth disease virus preparations permits to obtain separately positive (2% phosphotungstic acid solution, pH 3.0) and negative (2% PTA solution, pH 6.8 +/- 8.0) stainings. When a 3--4% PTA solution, pH 6.8 +/- 8.0 is used, simultaneous positive and negative staining of each virion is possible which characterizes the functional heterogeneity of the virion protein membrane in interaction with PTA anions.

Microwave-assisted hydrolysis of polysaccharides over polyoxometalate clusters.

Polyoxometalate (POM) clusters were utilized as recyclable acid catalysts and microwave-absorbing agents for the microwave-assisted hydrolysis of corn starch and crystalline cellulose. Phosphotungstic (PW) and silicotungstic (SiW) acids showed high hydrolyzing activity, while phosphomolybdic acid (PMo) showed lower glucose stability. The PW catalyst could be recycled by ether extraction at least 4 times without changing its catalytic activity. The addition of PW could reduce the energy demand required for running the hydrolysis by 17-23%. The dielectric property of the aqueous PW solution was important for increasing the microwave-absorption capability of the reaction system and reducing the energy consumption.

[Analytical application of phosphotungstic acid complexes. Fabrication and characterisation of membrane selective electrodes for some H2 antihistaminics]. / Complecsi ai acidului fosfowolframic cu aplicatii analitice. Constructia si caracterizarea unor electrozi membrana selectivi pentru unele antihistaminice H2.

PVC matrix membrane selective electrodes for ranitidine, nizatidine and famotidine, based on sparingly soluble complexes, were prepared and characterized. The optimum functional pH range, response time, selectivity and lifetime were determined for each of the built electrodes. The linear range, precision and accuracy of each method were obtained by statistical interpretation of experimental results, while the limit of detection and thelimit of quantification were determined by a graphical method. All these electrodes were applied for the direct quantitative potentiometric determination of ranitidine hydrochloride, nizatidine and famotidine in pharmaceutical formulations.