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1.
Serum zinc, copper and iron status of children with coeliac disease on three months of gluten-free diet with or without four weeks of zinc supplements: a randomised controlled trial.
Negi, K, Kumar, R, Sharma, L, Datta, SP, Choudhury, M, Kumar, P
Tropical doctor. 2018;(2):112-116
Abstract
Data about the effect of zinc supplementation with gluten-free diet on normalisation of plasma zinc, copper and iron in patients with coeliac disease are scanty. We evaluated the effect of zinc supplementation on serum zinc, copper and iron levels in patients with coeliac disease, by randomising 71 children newly diagnosed with coeliac disease into two groups: Group A = gluten-free diet (GFD); and Group B = gluten-free diet with zinc supplements (GFD +Zn). The rise in iron and zinc was significantly higher in the latter, but the mean rise of copper levels was slightly higher in the former, but the difference was not significant.
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2.
Enhancement in anti-tubercular activity of indole based thiosemicarbazones on complexation with copper(I) and silver(I) halides: Structure elucidation, evaluation and molecular modelling.
Khan, A, Jasinski, JP, Smolenski, VA, Hotchkiss, EP, Kelley, PT, Shalit, ZA, Kaur, M, Paul, K, Sharma, R
Bioorganic chemistry. 2018;:303-318
Abstract
A series of monomeric tetrahedral complexes of stoichiometry, [MX(HL)(Ph3P)2] (In case of M = Cu, H1L, X = I, 1; Br, 2; Cl, 3; H3L, X = I, 4; Br, 5; Cl, 6; H4L, X = I, 7; Br, 8; Cl, 9 and in case of M = Ag, H1L, X = Cl, 13; Br, 14; H2L, X = Cl, 15, Br 16; H3L, X = Cl, 17, Br, 18) were synthesized by the reaction of copper (I) or silver (I) halides with indole-3-thiosemicarbazone (H1L) or 5-methoxy indole-3-thiosemicarbazone (H2L) or 5-methoxy indole-N1-methyl-3-thiosemicarbazone (H3L), whereas dimers of stoichiometry, [Cu2(μ-X)2(η1-S-H2L)2(Ph3P)2] (X = I, 10; Br, 11; Cl, 12) were obtained by the reaction of copper (I) halides with indole-N1-methyl-3-thiosemicarbazone (HIntsc-N1-Me, H2L). The synthesized complexes were characterized using NMR (1H and 13C) and single crystal X-ray diffraction (H2L, 3, 7, 8, 10, 11 and 13) as well as elemental analysis. Anti- M. tuberculosis activity of ligands (H1L-H4L) and their metal complexes (1-18) were evaluated against M. tuberculosis H37RV strain ATCC 27294. It has been observed that there is unusual enhancement in anti TB activity of these ligands on complexation with copper (I) and silver (I). Molecular modelling studies in the active binding site are also giving complementary theoretical support for the experimental biological data acquired.
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3.
Corchorus olitorius and Urtica pilulifera extracts alleviate copper induced oxidative damage and genotoxicity in tomato.
İşeri, ÖD, Körpe, DA, Sahin, FI, Haberal, M
Acta biologica Hungarica. 2018;(3):300-312
Abstract
Copper cause oxidative damage in plant cells, and plant extracts are the sources of free radical scavengers. We tested the hypothesis that whether Corchorus olitorius (jute) and Urtica pilulifera (Roman nettle) seed extract treatments of germinated seeds affect copper induced oxidative and genotoxic damage or antioxidant response in tomato. Seedlings were exposed to toxic copper concentration (30 ppm) for 7 days. In one experimental group (treatment 1), extract (100 μg mL-1) was added to media. In the other group (treatment 2), tomato seeds were pre-soaked by the extract (100 μg mL-1) prior to germination and copper application. Malondialdehyde and endogenous H2O2 levels in the groups treated with extract and copper were significantly lower than that of the untreated groups. Pre-soaking seeds with the nettle extract solution significantly enhanced catalase activity under unstressed condition. Jute treatment also enhanced catalase activity under copper stress. Ascorbate peroxidase activity remained at unstressed level in copper treated groups. Extract treatments significantly decreased copper induced DNA damage in root nuclei. Jute seed extract contained salicylic acid and quercetin which can be correlated with the evoked effects. We demonstrated protective effect of plant extract treatments against copper stress of tomato seedlings prior to germination or during seedling development.
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4.
Paradoxical effects of density on measurement of copper tolerance in Silene paradoxa L.
Capuana, M, Colzi, I, Buccianti, A, Coppi, A, Palm, E, Del Bubba, M, Gonnelli, C
Environmental science and pollution research international. 2018;(2):1331-1339
Abstract
This work investigated if the assessment of tolerance to trace metals can depend on plant density in the experimental design. A non-metallicolous and a metallicolous populations of Silene paradoxa were hydroponically cultivated at increasing density and in both the absence (-Cu conditions) and excess of copper (+Cu conditions). In -Cu conditions, the metallicolous population showed a lower susceptibility to plant density in comparison to the non-metallicolous one, explained by a higher capacity of the metallicolous population to exploit resources. In +Cu conditions, an alleviating effect of increasing density was found in roots. Such effect was present to a greater extent in the non-metallicolous population, thus making the populations equally copper-tolerant at the highest density used. In shoots, an additive effect of increasing plant density to copper toxicity was reported. Its higher intensity in the metallicolous population reverted the copper tolerance relationship at the highest plant densities used. In both populations, a density-induced decrease in root copper accumulation was observed, thus concurring to the reported mitigation in +Cu conditions. Our work revealed the importance of density studies on the optimization of eco-toxicological bioassays and of metal tolerance assessment and it can be considered the first example of an alleviating effect of increasing plant number on copper stress in a metallophyte.
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5.
Absorption Mechanisms of Iron, Copper, and Zinc: An Overview.
Nishito, Y, Kambe, T
Journal of nutritional science and vitaminology. 2018;(1):1-7
Abstract
Essential trace elements play pivotal roles in numerous structural and catalytic functions of proteins. Adequate intake of essential trace elements from the daily diet is indispensable to the maintenance of health, and their deficiency leads to a variety of conditions. However, excessive amounts of these trace elements may be highly toxic, and in some cases, may cause damage by the production of harmful reactive oxygen species. Homeostatic dysregulation of their metabolism increases the risk of developing diseases. Specific transport proteins that facilitate influx or efflux of trace elements play key roles in maintaining the homeostasis. Recent elucidation of their crucial functions significantly facilitated our understanding of the molecular mechanisms of iron (Fe), copper (Cu), and zinc (Zn) absorption in the small intestine. This paper summarizes their absorption mechanisms, with a focus on indispensable functions of the molecules involved in it, and briefly discusses the mechanisms of homeostatic control of each element at the cellular and systemic levels.
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6.
Revisiting the catalytic mechanism of Mo-Cu carbon monoxide dehydrogenase using QM/MM and DFT calculations.
Xu, K, Hirao, H
Physical chemistry chemical physics : PCCP. 2018;(28):18938-18948
Abstract
Previous density functional theory (DFT) studies have shown that the release of the produced carbon dioxide (CO2) from an active-site cluster is a thermodynamically or kinetically difficult step in the enzymatic carbon monoxide (CO) oxidation catalyzed by Mo-Cu carbon monoxide dehydrogenase (Mo-Cu CODH). To better understand the effect of the protein environment on this difficult CO2 release step as well as other reaction steps, we applied hybrid quantum mechanics and molecular mechanics (QM/MM) calculations to the Mo-Cu CODH enzyme. The results show that in the first step, the equatorial Mo[double bond, length as m-dash]O group in the active-site cluster attacks the nearby CO molecule bound to the Cu site. Afterward, a stable thiocarbonate intermediate is formed in which the CO2 molecule is embedded and the copper-S(μ-sulfido) bond is broken. A free CO2 molecule, i.e., the final product, is then released from the active-site cluster, not directly from the thiocarbonate intermediate but via a previously formed intermediate that also contains CO2 but retains the Cu-S(μ-sulfido) bond. In contrast to the previous DFT results, the calculated barrier for this process was low in our QM/MM calculations. An additional QM/MM analysis of the barrier height showed that the effect of the protein environment on this barrier lowering is not very large. We found that the reason for the low barrier obtained by QM/MM is that the barrier for CO2 release is already not high at the DFT level. These results allow us to conclude that the CO oxidation reaction passes through the formation of a thiocarbonate intermediate, and that the subsequent CO2 release is kinetically not difficult. Nevertheless, the protein environment has an important role to play in making the latter process thermodynamically favored. No low-barrier pathway for the product release could be obtained for the reaction of n-butylisocyanide, which is consistent with the experimental fact that n-butylisocyanide inhibits Mo-Cu CODH.
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7.
Comparative study of Cu-based bimetallic oxides for Fenton-like degradation of organic pollutants.
Wang, Q, Ma, Y, Xing, S
Chemosphere. 2018;:450-456
Abstract
In order to provide useful information for the rational design of effective Fenton-like catalyst, a series of Cu-based bimetallic oxides were synthesized and their Fenton-like performances for the degradation of Orange II and ciprofloxacin were compared. The structure, chemical oxidation state, surface charge property and redox ability of the catalysts were also investigated by different characterization techniques. Among them, NiCu exhibited the highest adsorption capacity towards Orange II and the highest activity for the production of OH from H2O2 decomposition, which could be attributed to its high surface area and highly positively charged surface. However, FeCu exhibited the highest activity for the degradation of Orange II. The reason might be that FeCu has more unpaired electrons and higher redox ability, thus promoting the activation of adsorbed Orange II through the electron transfer process. By contrast, NiCu exhibited the highest activity for the removal of ciprofloxacin because ciprofloxacin was mainly degraded by OH. Finally, the main degradation intermediates of Orange II and ciprofloxacin were determined by liquid chromatography-mass spectrometry.
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8.
Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases.
Lanza, V, Milardi, D, Di Natale, G, Pappalardo, G
Current medicinal chemistry. 2018;(4):525-539
Abstract
BACKGROUND There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) chelating molecules as potential drug candidates in neurodegeneration. METHODS Starting from the well-known harmful relationships existing between the dyshomeostasis and mis-management of metals and AD onset, we surveyed the experimental work reported in the literature, which deals with the repositioning of metal-chelating drugs in the field of neurodegenerative diseases. The reviewed papers were retrieved from common literature and their selection was limited to those describing the biomolecular aspects associated with neuroprotection. In particular, we emphasized the copper(II) coordination abilities of the selected drugs. RESULTS Copper, together with zinc and iron, are known to play a key role in regulating neuronal functions. Changes in copper homeostasis are crucial for several neurodegenerative disorders. The studies included in this review may provide an overview on the current strategies aimed at repurposing copper (II) chelating drugs for the treatment of neurodegenerative disorders. Starting from the exemplary case of clioquinol repurposing, we discuss the challenge and the opportunities that repurposing of other metal-chelating drugs may provide (e.g. PBT-2, metformin and cyclodipeptides) in the treatment of neurodegenerative disease. CONCLUSIONS In order to improve the success rate of drug repositioning, comprehensive studies on the molecular mechanism and therapeutic efficacy are still required. The present review upholds that drug repurposing makes significant advantages over drug discovery since repositioned drugs had already passed the safety and toxicity tests. Promising drug candidates in neurodegenerative diseases may be represented by copper chelating classes of drugs, provided that sufficient details on their mechanism of action are available to encourage further investigations and clinical trials.
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9.
Iron and Copper Active Sites in Zeolites and Their Correlation to Metalloenzymes.
Snyder, BER, Bols, ML, Schoonheydt, RA, Sels, BF, Solomon, EI
Chemical reviews. 2018;(5):2718-2768
Abstract
Metal-exchanged zeolites are a class of heterogeneous catalysts that perform important functions ranging from selective hydrocarbon oxidation to remediation of NO x pollutants. Among these, copper and iron zeolites are remarkably reactive, hydroxylating methane and benzene selectively at low temperature to form methanol and phenol, respectively. In these systems, reactivity occurs at well-defined molecular transition metal active sites, and in this review we discuss recent advances in the spectroscopic characterization of these active sites and their reactive intermediates. Site-selective spectroscopy continues to play a key role, making it possible to focus on active sites that exist within a distribution of inactive spectator metal centers. The definition of the geometric and electronic structures of metallozeolites has advanced to the level of bioinorganic chemistry, enabling direct comparison of metallozeolite active sites to functionally analogous Fe and Cu sites in biology. We identify significant parallels and differences in the strategies used by each to achieve high reactivity, highlighting potentially interesting mechanisms to tune the performance of synthetic catalysts.
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10.
64CuCl2 PET/CT in Prostate Cancer Relapse.
Piccardo, A, Paparo, F, Puntoni, M, Righi, S, Bottoni, G, Bacigalupo, L, Zanardi, S, DeCensi, A, Ferrarazzo, G, Gambaro, M, et al
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;(3):444-451
Abstract
Our objective was to evaluate the biodistribution, kinetics, and radiation dosimetry of 64CuCl2 in humans and to assess the ability of 64CuCl2 PET/CT to detect prostate cancer (PCa) recurrence in patients with biochemical relapse. Methods: We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external-beam radiation therapy. All patients underwent 64CuCl2 PET/CT, 18F-choline PET/CT, and multiparametric MRI within 15 d of each other. Experienced readers interpreted the images, and the detection rate (DR) of each imaging modality was calculated. Histopathology, when available; clinical or laboratory response; and multidisciplinary follow-up were used to confirm the site of disease. In parallel, biodistribution, kinetics of the lesions, and radiation dosimetry of 64CuCl2 were evaluated. Results: From a dosimetric point of view, an administered dose of 200 MBq for 64CuCl2 translated into a 5.7-mSv effective dose. Unlike 18F-choline, 64CuCl2 was not excreted or accumulated in the urinary tract, thus allowing thorough pelvic exploration. The maximum 64CuCl2 uptake at the sites of PCa relapse was observed 1 h after tracer injection. In our cohort, 64CuCl2 PET/CT proved positive in 41 of 50 patients, with an overall DR of 82%. The DRs of 18F-choline PET/CT and multiparametric MRI were 56% and 74%, respectively. The difference between the DRs of 64CuCl2 PET/CT and 18F-choline PET/CT was statistically significant (P < 0.001). Interestingly, on considering prostate-specific antigen (PSA) value, 64CuCl2 PET/CT had a higher DR than 18F-choline PET/CT in patients with a PSA of less than 1 ng/mL. Conclusion: The biodistribution of 64CuCl2 is more suitable than that of 18F-choline for exploring the pelvis and prostatic bed. The 64CuCl2 effective dose is like those of other established PET tracers. In patients with biochemical relapse and a low PSA level, 64CuCl2 PET/CT shows a significantly higher DR than 18F-choline PET/CT.