DNA interaction,anti-proliferative effect of copper oxide nanocolloids prepared from metallosurfactant based microemulsions acting as precursor,template and reducing agent

In the present study, we have synthesized mixed cuprous/copper oxide nanosuspensions by metallosurfactant based microemulsion technique. Three metallosurfactants were synthesized which includes two non-ionic double chained metallosurfactants with C₁₂, C₁₆ chains with coordinated copper i.e. Cudda and Cuhexa, respectively. Another cationic double chained metallosurfactant with loosely bound metal (Cuctac) was also prepared. The prepared metallocomplexes were characterized using FTIR, elemental analysis, and NMR. The effect of the position of metallosurfactant in microemulsion on the fabrication and properties of nanosuspensions was elucidated. In this method, no external reducing agent and capping agent were added and tween 80 acted both as reducing and stabilizing agent for the nanoparticles. The synthesized nanoparticles were characterized and it was observed that mixed copper and cuprous oxide particles are present in colloidal suspension for all the three studied metallosurfactants. The kinetics of formation of mixed copper/cuprous oxide nanosuspensions (Ns) and their stability was estimated using Uv-visible spectroscopy. Further, the binding and interactions of copper nanosuspensions with calf Thymus DNA (CT-DNA) were assessed using Uv–vis spectroscopy, circular dichroism and gel electrophoresis. Additionally, the antioxidant activity of the Cu Ns was checked using DPPH assay. The role of positive charge on nanoparticles as evaluated from Zeta potential was responsible for DNA affinity. The DNA conformational changes in the presence of nanosuspensions and relevant scavengers were investigated. Further, the anti-proliferative activity of copper Ns was assessed using HeLa cells and Cuhexa derived Ns were proved to be active with highest activity at a low concentration and were nontoxic towards normal cell lines. In summary, this work demonstrates a softer approach for the synthesis of copper nanosuspensions with a size range of 2–5?nm and evaluated the role of type and structure of metallosurfactant on size, stability of particles and anti-proliferative activity.     

Integrated analytical techniques with high sensitivity for studying brain translocation and potential impairment induced by intranasally instilled copper nanoparticles

Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing attention. In this paper, integrated analytical techniques with high sensitivity were used to study the brain translocation and potential impairment induced by intranasally instilled copper nanoparticles (CuNPs). Mice were exposed to CuNPs in three doses (1, 10, 40 mg/kg bw). The body weight of mice decreased significantly in the 10 and 40 mg/kg group (p < 0.05) but recovered slightly within exposure duration. Inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that CuNPs could enter the brain. Altered distribution of some important metal elements was observed by synchrotron radiation X-ray fluorescence (SRXRF). H&E staining and immunohistochemical analysis showed that CuNPs produced damages to nerve cells and astrocyte might be the one of the potential targets of CuNPs. The changes of neurotransmitter levels in different brain regions demonstrate that the dysfunction occurred in exposed groups. These data indicated that CuNPs could enter the brain after nasal inhalation and induced damages to the central nervous system (CNS). Integration of effective analytical techniques for systematic investigations is a promising direction to better understand the biological activities of nanomaterials.     

瞬时受体电位通道A1和瞬时受体电位通道M8在冷过敏中的作用

背景 冷过敏是炎性痛和神经病理性疼痛的一个常见症状,其内在机制尚不清楚. 目的 阐明瞬时受体电位通道A1 （transient receptor potential cation channel,subfamily A,member 1,TRPA1）和瞬时受体电位通道M8（transient receptor potential melastatin 8,TRPM8）参与冷过敏的机制. 内容 综述TRPA1和TRPM8的分子结构和门控机制及其在有害的冷、炎性痛和神经病理性疼痛的冷过敏形成、维持中的作用等方面的研究. 趋向 深入研究TRPA1和TRPM8在冷过敏发生中的作用,有助于阐明冷过敏的机制,并为开发拮抗剂提供理论依据.     

The phosphoproteome and its physiological dynamics in Staphylococcus aureus

Phosphorylation events on proteins during growth and stress/starvation can represent crucial regulation processes inside the bacterial cell. Therefore, serine, threonine and tyrosine phosphorylation patterns were analyzed by two powerful complementary proteomic methods for the human pathogen Staphylococcus aureus. Using 2D-gel analysis with a phosphosensitive stain (Pro-Q Diamond) and gel-free titanium dioxide based phosphopeptide enrichment, 103 putative phosphorylated proteins with successfully mapped 68 different phosphorylation sites were found in the soluble proteome of S. aureus. Additionally, in a proof of concept study, 8 proteins phosphorylated on arginine residues have been identified. Most important for functional analyses of S. aureus, proteins related to pathogenicity and virulence were found to be phosphorylated: the virulence regulator SarA, the potential antimicrobial target FbaA and the elastin-binding protein EbpS. Besides newly identified phosphorylation sites we compared our dataset with existing data from literature and subsequent experiments revealed additional phosphorylation events on highly conserved localizations in FbaA. Differential analysis of phosphorylation signals on the 2D-gels showed significant changes in phosphorylation under different physiological conditions for 10 proteins. Among these, we were able to detect newly appearing signals for phosphorylated isoforms of FdaB and HchA under nitrosative stress conditions.     

胃肠道平滑肌起搏电流产生机制的研究进展

越来越多的研究结果表明,Cajal间质细胞是胃肠道平滑肌慢波电位和自发性节律性收缩活动的起搏细胞.关于Cajal间质细胞起搏电流产生机制的研究近来进展很快,但仍存在一些分歧.本文就目前关于起搏电流的产生及传播机制的研究进展作一综述.     

High-performance ion-exchange chromatography with in-line complexation of bisphosphonates and their quality control in pharmaceutical preparations

An ion-exchange chromatographic method using an anion-exchange column was developed for the analysis of a number of bisphosphonates. The bisphosphonates were in-line complexed by copper(II) ions and added to the acidic eluent, to yield an UV-absorbing complex. Chromatographic parameters were studied for eight different bisphosphonates, particularly amino-1-hydroxyalkyl-1,1-bisphosphonates; special attention was paid to the relationship between retention and complex formation. The method was applied to the quality control of pamidronate injection concentrate and olpadronate tablets. The lower detection limit was 8 ng of disodium pamidronate, and the inter-assay precision was 1.0% for both pamidronate and olpadronate standard solutions and 1.8% for a 3 mg ml⁻¹ disodium pamidronate injection concentrate. The method was compared with a previously described ion-exchange chromatographic method with conductivity detection, without copper(II) ions in the eluent.     

Autocatalytic reduction of Cu(II) to copper by Co(II) studied by electrochemical quartz crystal microgravimetry in a wall jet cell

Electrochemical Quartz Crystal Microgravimetry (EQCM) studies were carried out in a new type of electroless copper plating solution containing Co(II)-ethylenediamine species as a reducing agent for Cu(II)-ethylenediamine complex. The rates of partial reactions of Cu(II) reduction and Co(II) oxidation were studied as a function of the electrode potential (?0.3 V to 0.05 V vs. SHE) under stopped-flow and wall jet conditions. The increase in the rate of partial reactions and the overall process under wall jet conditions suggests diffusion limitations occur in the transport of reacting species (Cu(II) and Co(II)) to the electrode and/or inhibiting products of reaction (Co(III) and ethylenediamine) to the bulk of the solution. Anodic dissolution of copper starts at 0.0 V.     

Surface protection of copper by azoles in borate buffers-voltammetric and impedance analysis

The inhibitory action of five azoles namely benzotriazole (BTA), mercaptobenzothiazole (MBT), benzimidazole (BIMD), mercaptobenzimidazole (MBIMD) and thiadiazole (TDA) on copper was examined in sodium borate solution of pH 6.4, 8.4 and 10.4 using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). A considerable drop off in the corrosion rate of copper was detected in the presence of the investigated compounds. CV showed that the inhibitors were of mixed type that they affect both the anodic and cathodic currents. Impedance spectra were characterized in terms of the charge transfer resistance and transport of copper ions through the oxide layer. The results indicate that the surface layer is of dielectric nature, and its protection increases with increasing inhibitor concentration and solution pH. On the basis of calculated adsorption data the process was concluded as chemisorption. Some quantum chemical parameters were also calculated using ab initio Hartree–Fock 6-31G*basis set and were used to complement the experimental results. The relative inhibition efficiencies of the azoles in controlling the copper corrosion was found to be in order of MBT > TDA > MBIMD≈BIMD > BTA.     

Modulation of polymorphonuclear leukocyte responsiveness by copper (II)2 (niflumate)4

Antiinflammatory activities and modulations of PMNL responses produced by treatment with tetrakis--2-[3-(trifluoromethyl)-phenyl] aminonicotinatodicopper (II) [Cu(II)₂(niflumate)₄] and niflumic acid were studied in isologous serum-induced rat pleurisy. Doses of 10 or 30 mg/kg (35 or 106 µmol/kg) of niflumic acid or Cu(II)₂ (niflumate)₄ (8 or 23 µmol/kg) caused significant (p < 0.01) reductions in pleural exudate and number of polymorphonuclear leukocytes (PMNLs) in the exudate. While both doses of Cu(II)₂(niflumate)₄ produced significant dose-related reductions in both parameters, only the higher dose of niflumic acid produced a significant dose-related reduction in both parameters. Boyden chamber measurements of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) chemotaxis by PMNLs incubated with 10 or 30 µg/ml niflumic acid (35 or 106 nmol/ml) or Cu(II)₂(niflumate)₄ (8 or 23 nmol/ml) were significantly (p < 0.01 to p < 0.001) decreased in dose-related fashions. Chemotaxis of PMNLs from pleuritic rats treated orally with 10 or 30 mg/kg niflumic acid or Cu(II)₂(niflumate)₄ was significantly (p < 0.001) inhibited by the larger dose of niflumic acid and both doses of Cu(II)₂(niflumate)₄. Opsonized zymosan (OZ)-stimulated chemiluminescence (CL) of PMNLs from pleuritic rats treated orally with these same doses of niflumic acid or Cu(II)₂(niflumate)₄ was only significantly (p < 0.05 or p < 0.01 respectively) decreased by the larger doses. Superoxide (O ₂ ^- ) production by these cells was significantly decreased by the larger dose of niflumic acid (p < 0.05) while both doses of Cu(II)₂(niflumate)₄ produced significant (p < 0.05 to p < 0.01) decreases. Recovery of the decreased PMNL response in burned rats was also studied following treatment with these two compounds. Oral treatment of non-burned rats with 1 mg/kg niflumic acid (4 µmol/kg) or Cu(II)₂(niflumate)₄ (1 µmol/kg) did not affect OZ-stimulated O ₂ ^- production while decreased O ₂ ^- production in non-treated scald-burned rats was reversed by oral treatment with either niflumic acid or Cu(II)₂(niflumate)₄. It is concluded that Cu(II)₂(niflumate)₄ is a more effective antiinflammatory agent than niflumic acid and more effective modulation of PMNL responsiveness may explain its beneficial antipleuritic and burn-injury recovery effects. Formation of the copper complex of niflumic acidin vivo may also account for its beneficial antiinflammatory effects and recovery of depressed PMNL responsiveness in burned rats.