Cu(II) Binding Increases the Soluble Toxicity of Amyloidogenic Light Chains

Light chain amyloidosis (AL) is caused by the aberrant overproduction of immunoglobulin light chains (LCs). The resulting abnormally high LC concentrations in blood lead to deposit formation in the heart and other target organs. Organ damage is caused not only by the accumulation of bulky amyloid deposits, but extensive clinical data indicate that circulating soluble LCs also exert cardiotoxic effects. The nematode C. elegans has been validated to recapitulate LC soluble toxicity in vivo, and in such a model a role for copper ions in increasing LC soluble toxicity has been reported. Here, we applied microscale thermophoresis, isothermal calorimetry and thermal melting to demonstrate the specific binding of Cu2+ to the variable domain of amyloidogenic H7 with a sub-micromolar affinity. Histidine residues present in the LC sequence are not involved in the binding, and yet their mutation to Ala reduces the soluble toxicity of H7. Copper ions bind to and destabilize the variable domains and induce a limited stabilization in this domain. In summary, the data reported here, elucidate the biochemical bases of the Cu2+-induced toxicity; moreover, they also show that copper binding is just one of the several biochemical traits contributing to LC soluble in vivo toxicity.

Effects of coupled-/soluble- Copper generating from Copper-doped Titanium Dioxide Nanotubes on Cell Response

Background: Endothelialization in vitro is a very common method for surface modification of cardiovascular materials. However, mature endothelial cells are not suitable because of the difficulty in obtaining and immunogenicity. Methods: In this work, we determined the appropriate amount of copper by constructing a copper-loaded titanium dioxide nanotube array that can catalyze the release of nitric oxide, compared the effects of coupled-/soluble- copper on stem cells, and then induced stem cells to differentiate into endothelial cells. Results: The results showed that it had a strong promotion effect on the differentiation of stem cells into endothelial cells which might be used for endothelialization in vitro Conclusions: SEM and EDS results prove that a high content of copper ions are indeed doped onto the surface of nanotubes with small amounts of Cu release. The release of NO confirms that the release of several samples within a period of time is within the physiological concentration

The green, ultrafine cellulose-based porous nanofibrous membranes for efficient heavy metal ion removal through incorporation of chitosan by various electrospinning ways

The rapid global industrialization worsens the contamination of heavy metals in aquatic ecosystems on the earth. In this study, the green, ultrafine cellulose-based porous nanofibrous membranes for efficient heavy metal removal through incorporation of chitosan by the conventional and core-shell electrospinning ways were firstly obtained. The relations among parameters of electrospun solution, micro-morphology and porosity for nanofibers, the variation of chemical active sites and adsorption performance of biocomposite nanofibrous membranes for conventional and core-shell electrospinning as well as the adsorption effect factors of copper ions including initial concentration, pH of solution and interaction time were comprehensively investigated. The results show that the average diameter for conventional and core-shell ultrafine nanofibers at 50% chitosan and 30% chitosan loading can achieve 56.22 nm and 37.28 nm, respectively. The core-shell cellulose acetate/chitosan (CA/CS) biocomposite nanofibrous membranes induced the surface aggregation of copper ions to impede the further adsorption. The more uniform distribution for chemical adsorption sites can be obtained by the conventional single-nozzle electrospinning than by the core-shell one, which promotes the adsorption performance of copper ions and decreases the surface shrinkage of nanofibrous membranes during adsorption. The 30% CS conventional nanofibrous membranes at the pH=5 aqueous solution showed the optimum adsorption capacity of copper ions (86.4 mg/g). The smart combination of renewable biomass with effective chemical adsorptive sites, the electrospinning technology with interwoven porous structure and the adsorption method with low cost and facile operation shows a promising prospect for water treatment.

Design, Synthesis, Biological Evaluation and Molecular Docking Studies of 5-fluorouracil-dithiocarbamate Conjugates

In this paper, a series of novel 5-fluorouracil-dithiocarbamate conjugates were designed, synthesized and evaluated in vitro . The results of cytotoxicity assays illuminated that these conjugates had anti-tumor activity against B16, Hela and U87MG, and compound P3 exhibited excellent growth inhibition against U87MG cells. Interestingly, the cytotoxicity of these conjugates was significantly increased when combined with copper ions. Meanwhile, colony-formation assays, transwell migration assays, cell apoptosis assays and cell cycle distribution assays were performed to explore the anti-tumor mechanism of conjugates. Compound P3 and P4 exhibited good biological activity in above four experiments when combined with copper ions. Especially, P3 displayed better bioactivity compared to the other three compounds. These results indicated that conjugates might be metabolized in the cells to produce dithiocarbamates, then metabolites formed complexes with copper ions, generating anti-tumor effects. Furthermore, conjugates and their metabolized dithiocarbamate derivatives were investigated by molecular docking, the results exhibited that P3 had the strongest interaction with the proteins 6CCY and 5T92, which was consistent with the obtained results of cell experiments. Compound P3 might be a potential lead-compound for the treatment of breast cancer and glioma. Further research in vivo about these compounds would be performed in our following work.

Modified Activated Carbon for Copper Ion Removal from Aqueous Solution

Because of increasing environmental awareness, it is becoming more important to remove harmful elements from water solutions. This study used activated carbon (AC) derived from waste wood-based panels as the base material, oxidized with nitric acid (OAC), and grafted with iminodiacetic acid (IDA-OAC) to improve the adsorption capacity and affinity for metals. The characterization of AC, OAC, and IDA-OAC was conducted via FTIR, SEM, N2 adsorption and desorption analysis, elemental analysis, Boehm titration, and point of zero charge (PZC). The instrument studies proved the modified increasing of the functional groups of the adsorbents. Moreover, batch and column experiments were conducted to evaluate the ability of the three adsorbents to remove copper ions from aqueous solution. In batch sorption, IDA-OAC had the highest adsorption capacity (84.51 mg/g) compared to OAC (54.74 mg/g) and AC (24.86 mg/g) at pH 5. The breakthrough point (Ct/Ci = 0.05) of copper ions for IDA-OAC occurred much later than AC in the column experiment (AC = 19 BV, IDA-OAC = 52 BV). The Langmuir isotherm and pseudo-second-model kinetics modeling could better fit with the data obtained from the batch sorption of AC, OAC, and IDA-OAC. The significant capacity and reusability of IDA-OAC displayed high applicability for water treatment.

Probable Reasons for Neuron Copper Deficiency in the Brain of Patients with Alzheimer’s Disease: The Complex Role of Amyloid

Alzheimer’s disease is a progressive neurodegenerative disorder that eventually leads the affected patients to die. The appearance of senile plaques in the brains of Alzheimer’s patients is known as a main symptom of this disease. The plaques consist of different components, and according to numerous reports, their main components include beta-amyloid peptide and transition metals such as copper. In this disease, metal dyshomeostasis leads the number of copper ions to simultaneously increase in the plaques and decrease in neurons. Copper ions are essential for proper brain functioning, and one of the possible mechanisms of neuronal death in Alzheimer’s disease is the copper depletion of neurons. However, the reason for the copper depletion is as yet unknown. Based on the available evidence, we suggest two possible reasons: the first is copper released from neurons (along with beta-amyloid peptides), which is deposited outside the neurons, and the second is the uptake of copper ions by activated microglia.

The Effect of Freeze-Thaw Cycling and the Initial Mass of Water on the Unfrozen Water Content of Calcium Bentonites Modified by Copper Ions

This research was conducted with the use of the DSC method; it involved the examination of the unfrozen water content in two model (source) calcium bentonites (≥75% smectite), after one to three freeze-thaw cycles in the natural state, as well as after the ion exchange for a potentially toxic element (Cu2+). The freeze-thaw cycles do not affect the unfrozen water content at a given negative temperature in a statistically significant manner. However, a statistically significant influence of temperature, the initial mass of the water, and the clay type on the change of the unfrozen water content was found. Moreover, the empirical models of predicting the unfrozen water in the bentonite after the exchange for Cu2+ ion were created, for which the parameter was the mass of the water and the mass of the dry soil, at the temperature of −2 °C.

Copper Surface Treatment Method with Antibacterial Performance Using “Super-Spread Wetting” Properties

In this work, a copper coating is developed on a carbon steel substrate by exploiting the superwetting properties of liquid copper. We characterize the surface morphology, chemical composition, roughness, wettability, ability to release a copper ion from surfaces, and antibacterial efficacy (against Escherichia coli and Staphylococcus aureus). The coating shows a dense microstructure and good adhesion, with thicknesses of approximately 20–40 µm. X-ray diffraction (XRD) analysis reveals that the coated surface structure is composed of Cu, Cu2O, and CuO. The surface roughness and contact angle measurements suggest that the copper coating is rougher and more hydrophobic than the substrate. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) measurements reveal a dissolution of copper ions in chloride-containing environments. The antibacterial test shows that the copper coating achieves a 99.99% reduction of E. coli and S. aureus. This study suggests that the characteristics of the copper-coated surface, including the chemical composition, high surface roughness, good wettability, and ability for copper ion release, may result in surfaces with antibacterial properties.

Adsorptive Removal of Copper from Waste Water Using Biomass & Biochar Based Materials

Heavy metal contamination has been one of the primary environmental concerns for many years in most developing countries. As the industries continue to search for low-cost and efficient adsorbents to treat their effluents contaminated with these toxic metal ions, biomass-based adsorbents have gained much attention. This work exploits such ten different biomass-based adsorbents (namely, Karanja de-oiled cake, Neem de-oiled cake, Neem leaves, Moringa Leaves, Bagasse, Mango Kernel, Wheat Bran, Eucalyptus, Fly ash, and Corn cob) for adsorption of copper ions in particular. Further, selected adsorbents (namely Karanja de-oiled cake, Neem de-oiled cake, Bagasse, Wheat Bran and Mango Kernel) were taken to the next stage and modified to biochar and tested again for copper removal. Among the biomass-based adsorbents, the highest adsorption capacity was observed for Neem de-oiled cake (equal to 9.6 mg/g). While for biochar-based adsorbents, Bagasse showed the highest adsorption capacity for copper (equivalent to 13.0 mg/g).