-
1.
Association Between the Change of Serum Copper and Ischemic Stroke: a Systematic Review and Meta-Analysis.
Zhang, M, Li, W, Wang, Y, Wang, T, Ma, M, Tian, C
Journal of molecular neuroscience : MN. 2020;(3):475-480
Abstract
Ischemic stroke is the most common stroke subtypes with all strokes. More and more studies found that serum copper was related to the ischemic stroke. However, the correlation between serum copper and ischemic stroke was inconsistent. We performed the meta-analysis to assess the association between the change of serum copper and ischemic stroke. Electronic databases were identified to search for relevant studies about serum copper and ischemic stroke from inception to February 28, 2019. Eight studies with a total of 777 participants were included into this meta-analysis. Because of high heterogeneity (I2 = 71%), we chose a random effect model. Our results showed the serum copper levels were significantly higher in ischemic stroke group compared with controls group (pooled mean difference, 1.25; 95% confidence intervals (CIs), 0.07-2.43; P = 0.04), in particular studies after the year of 2009 (I2 = 0%; pooled mean difference, 2.16; 95% CI, 1.37-2.95; P < 0.00001). Serum copper was associated with ischemic stroke, and it may be one of the risk factors of ischemic stroke.
-
2.
Wilson disease.
Aggarwal, A, Bhatt, M
Current opinion in neurology. 2020;(4):534-542
Abstract
PURPOSE OF REVIEW The aim of this article is to review recent developments in the areas of the disease features and treatment of Wilson disease, and survey disorders that share its pathophysiology or clinical symptoms. RECENT FINDINGS Knowledge of the clinical spectrum of Wilson disease has expanded with recognition of patients who present in atypical age groups - patients with very early onset (<5 years) and those in whom symptoms present in mid-to-late adulthood. A disease phenotype with dominant psychiatric features and increased risk of cardiac problems and various sleep disorders have been identified.In addition to a better understanding of the phenotype of Wilson disease itself, features of some related disorders ('Wilson disease-mimics') have been described leading to a better understanding of copper homeostasis in humans. These disorders include diseases of copper disposition, such as mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratoderma syndrome, Niemann-Pick type C, and certain congenital disorders of glycosylation, as well as analogous disorders of iron and manganese metabolism.Outcomes for existing treatments, including in certain patient subpopulations of interest, are better known. Novel treatment strategies being studied include testing of bis-choline tetrathiomolybdate in phase 2 clinical trial as well as various preclinical explorations of new copper chelators and ways to restore ATP7B function or repair the causative gene. SUMMARY Recent studies have expanded the phenotype of Wilson disease, identified rare inherited metal-related disorders that resemble Wilson disease, and studied long-term outcomes of existing treatments. These developments can be expected to have an immediate as well as a long-term impact on the clinical management of the disease, and point to promising avenues for future research.
-
3.
Probing synergistic interplay between bio-inspired peptidomimetic chitosan-copper complexes and doxorubicin.
Pandit, A, Khare, L, Jahagirdar, D, Srivastav, A, Jain, R, Dandekar, P
International journal of biological macromolecules. 2020;:1475-1483
Abstract
The current investigation reports a novel and facile method for modification of low molecular weight chitosan (Cs) with guanidine moieties, aimed at enhancing its cellular interaction and thus augmenting its cellular internalization. Guadinylated chitosan-copper (Cs-Gn-Cu) chelates, based on copper-nitrogen co-ordination, were established. Characterization of chelates was conducted using 1H NMR, 13C NMR, XPS, XRD, TGA-DTA, and GPC techniques. Anticancer activity of formed chelates was confirmed against A549 cells using MTT assay. Experimental outcomes, for the first time, have provided an empirical evidence for synergistic interaction between the chelated polymer (Cs-Gn-Cu) and the established anti-cancer agent, Doxorubicin (Dox), based on analysis by the Chou Talalay method and estimation of their combination indices. ROS induction was demonstrated as the mechanism of action of the chelated polymer, which supplemented rapid destruction of cancerous cells by Dox. These findings strongly advocate the need for harnessing unexplored potential of these innovative metal polymer chelates in cases of Dox resistant lung cancer, wherein the polymeric system itself would serve as an anti-cancer agent.
-
4.
New insights into copper homeostasis in filamentous fungi.
Antsotegi-Uskola, M, Markina-Iñarrairaegui, A, Ugalde, U
International microbiology : the official journal of the Spanish Society for Microbiology. 2020;(1):65-73
-
-
Free full text
-
Abstract
Copper is a metal ion that is required as a micronutrient for growth and proliferation. However, copper accumulation generates toxicity by multiple mechanisms, potentially leading to cell death. Due to its toxic nature at high concentrations, different chemical variants of copper have been extensively used as antifungal agents in agriculture and medicine. Most studies on copper homeostasis have been carried out in bacteria, yeast, and mammalian organisms. However, knowledge on filamentous fungi is less well documented. This review summarizes the knowledge gathered in the last few years about copper homeostasis in the filamentous fungi Aspergillus fumigatus and Aspergillus nidulans: The mechanism of action of copper, the uptake and detoxification systems, their regulation at the transcriptional level, and the role of copper homeostasis in fungal pathogenicity are presented.
-
5.
Effects of copper on biological treatment of NMF- and MDG-containing wastewater from TFT-LCD industry.
Cheng, HH, Pien, TT, Lee, YC, Lu, IC, Whang, LM
Chemosphere. 2020;:127125
Abstract
This study aimed to evaluate the effects of copper on N-methylformamide (NMF)- and methyl diglycol (MDG)-containing wastewater treatment using batch experiments and a lab-scale anoxic-oxic (A/O) sequencing batch reactor (SBR). Batch experimental results indicated that aerobic degradation of NMF followed Monod-type kinetics. Copper inhibition on nitrification also followed Monod-type inhibition kinetics with copper-to-biomass ratio instead of copper concentration. Specific degradation rates of NMF and MDG under both aerobic and anoxic conditions decreased in the matrix of full-scale wastewater, and high copper dosage would further reduce the degradation rates. In the long-term presence of 0.5 mg/L copper, the A/O SBR could maintain stable and complete degradations of NMF and MDG, 95% of COD removal, and more than 50% of total nitrogen (TN) removal. High concentrations of copper spikes, including 40 mg/L and 110 mg/L, slowed down degradation rates for both NMF and MDG, but did not affect COD and TN removal efficiencies in the full 24 h-cycle operation. The long-term A/O SBR operation revealed that daily dosage of 0.5 mg/L copper was not detrimental to NMF/MDG degradations due to regularly wasting sludge, but 110 mg/L of copper spike obviously reduced NMF/MDG degradation rate although it could be recovered later by regularly wasting sludge and maintaining SRT at 20 days.
-
6.
From coins to cancer therapy: Gold, silver and copper complexes targeting human topoisomerases.
Ceramella, J, Mariconda, A, Iacopetta, D, Saturnino, C, Barbarossa, A, Caruso, A, Rosano, C, Sinicropi, MS, Longo, P
Bioorganic & medicinal chemistry letters. 2020;(3):126905
Abstract
Cancer is a complex issue and, even though the prevention basics and therapy have been implemented, it is still the second leading death cause worldwide. With the hope to discover new powerful and safer molecules to fight cancer, many researchers focused their attention on metal-based compounds, starting from the most famous and successfully employed anticancer drug, i.e. cisplatin. The current article aims to report the most recent discoveries about the use of gold, silver and copper complexes as antitumor agents, highlighting their influences on important enzymes, namely human topoisomerases. The latter are fundamental for the cell life and, if overexpressed, strongly implicated in cancer onset and progression. The identification of lead complexes targeting human topoisomerases and gifted with the appropriate chemical and pharmacological properties represents a fecund starting point to obtain new and more effective anticancer molecules.
-
7.
Copper and selenium status as biomarkers of neonatal infections.
Hackler, J, Wisniewska, M, Greifenstein-Wiehe, L, Minich, WB, Cremer, M, Bührer, C, Schomburg, L
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2020;:126437
Abstract
Neonatal infections are a major risk factor for neonatal mortality. A reliable diagnosis of early-onset sepsis (EOS) is hampered by the variable clinical presentations of the children. We hypothesized that changes in the Se or Cu status, or the biomarkers selenoprotein P (SELENOP) or ceruloplasmin (CP) alone or in combination may be informative of EOS. We generated a new human CP-specific non-competitive immunoassay (ELISA) suitable of analysing small sample volumes and validated the method with a commercial CP source. Using this novel CP assay, we analysed a case-control study of EOS (n = 19 control newborns, n = 18 suspected cases). Concentrations of Se, Cu, SELENOP, CP, interleukin-6 (IL-6), and C-reactive protein (CRP) along with the Cu/Se and CP/SELENOP ratios were evaluated by correlation analyses as biomarkers for EOS. Diagnostic value was estimated by receiver operating characteristic (ROC) curve analyses. The new CP-ELISA displayed a wide working range (0.10-6.78 mg CP/L) and low sample requirement (2 μL of serum, EDTA-, heparin- or citrate-plasma). Plasma CP correlated positively with Cu concentrations in the set of all samples (Pearson r = 0.8355, p < 0.0001). Three of the infected neonates displayed particularly high ratios of Cu/Se and CP/SELENOP, i.e., 3.8- to 6.9-fold higher than controls. Both the Cu/Se and the CP/SELENOP ratios correlated poorly with the early infection marker IL-6, but strongly and positively with the acute-phase protein CRP (Cu/Se-CRP: Spearman ϱ = 0.583, p = 0.011; CP/SELENOP-CRP: ϱ = 0.571, p = 0.013). The ROC curve analyses indicate that a combination of biomarkers for the Se and Cu status do not improve the early identification of EOS considerably. This study established a robust, highly precise, partly validated and scalable novel CP sandwich ELISA suitable for basic and clinical research, requiring minute amounts of sample. The ratio of circulating CP/SELENOP constitutes a promising new composite biomarker for detection of EOS, at least in a subset of severely diseased children.
-
8.
Selenium and Copper as Biomarkers for Pulmonary Arterial Hypertension in Systemic Sclerosis.
Sun, Q, Hackler, J, Hilger, J, Gluschke, H, Muric, A, Simmons, S, Schomburg, L, Siegert, E
Nutrients. 2020;(6)
Abstract
Circulating selenoprotein P (SELENOP) constitutes an established biomarker of Se status. SELENOP concentrations are reduced in inflammation and severe disease. Recently, elevated SELENOP levels have been suggested as diagnostic marker and therapeutic target in pulmonary arterial hypertension (PAH). We decided to re-evaluate this hypothesis. A group of healthy controls (n = 30) was compared with patients suffering from systemic sclerosis (SSc, n = 66), one third with SSc-related PAH. Serum was analysed for trace elements and protein biomarkers, namely SELENOP, glutathione peroxidase 3 (GPx3) and ceruloplasmin (CP). Compared to controls, patients with SSc-related PAH displayed reduced serum Se (91 ± 2 vs. 68 ± 2 µg/L) and SELENOP concentrations (3.7 ± 0.8 vs. 2.7 ± 0.9 mg/L), along with lower GPx3 activity (278 ± 40 vs. 231 ± 54 U/L). All three biomarkers of Se status were particularly low in patients with skin involvement. Serum Cu was not different between the groups, but patients with SSc-related PAH showed elevated ratios of Cu/Se and CP/SELENOP as compared to controls. Our data indicate that patients with SSc-related PAH are characterized by reduced Se status in combination with elevated CP, in line with other inflammatory diseases. Further analyses are needed to verify the diagnostic value of these TE-related biomarkers in PAH.
-
9.
Evaluating the Performance of a Non-Bonded Cu2+ Model Including Jahn-Teller Effect into the Binding of Tyrosinase Inhibitors.
Martins, LS, Lameira, J, Kruger, HG, Alves, CN, Silva, JRA
International journal of molecular sciences. 2020;(13)
Abstract
Tyrosinase (TYR) is a metalloenzyme classified as a type-3 copper protein, which is involved in the synthesis of melanin through a catalytic process beginning with the conversion of the amino acid l-Tyrosine (l-Tyr) to l-3,4-dihydroxyphenylalanine (l-DOPA). It plays an important role in the mechanism of melanogenesis in various organisms including mammals, plants, and fungi. Herein, we used a combination of computational molecular modeling techniques including molecular dynamic (MD) simulations and the linear interaction energy (LIE) model to evaluate the binding free energy of a set of analogs of kojic acid (KA) in complex with TYR. For the MD simulations, we used a dummy model including the description of the Jahn-Teller effect for Cu2+ ions in the active site of this enzyme. Our results show that the LIE model predicts the TYR binding affinities of the inhibitor in close agreement to experimental results. Overall, we demonstrate that the classical model provides a suitable description of the main interactions between analogs of KA and Cu2+ ions in the active site of TYR.
-
10.
Selenium and copper status - potential signposts for neurological remission after traumatic spinal cord injury.
Seelig, J, Heller, RA, Hackler, J, Haubruck, P, Moghaddam, A, Biglari, B, Schomburg, L
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2020;:126415
Abstract
INTRODUCTION Traumatic Spinal Cord Injury (TSCI) is a severe incident resulting in loss of motor and sensory function caused by complex pathological mechanisms including massive oxidative stress and extensive inflammatory processes. The essential trace elements selenium (Se) and copper (Cu) play crucial roles as part of the antioxidant defense. HYPOTHESIS Remission after TSCI is associated with characteristic dynamics of early changes in serum Cu and Se status. STUDY DESIGN Single-center prospective observational study. PATIENTS AND METHODS Serum samples from TSCI patients were analyzed (n = 52); 21 recovered and showed a positive abbreviated injury score (AIS) conversion within 3 months (G1), whereas 21 had no remission (G0). Ten subjects with vertebral fractures without neurological impairment served as control (C). Different time points (at admission, and after 4, 9, 12, and 24 h) were analyzed for total serum Se and Cu concentrations by total reflection X-ray fluorescence, and for Selenoprotein P (SELENOP) and Ceruloplasmin (CP) by sandwich ELISA. RESULTS At admission, CP and SELENOP concentrations were higher in the remission group (G1) than in the non-remission group (G0). Within 24 h, there were marginal changes in Se, SELENOP, Cu and CP concentrations in the groups of controls (C) and G0. In contrast, these parameters decreased significantly in G1. Binary logistic regression analysis including Cu and Se levels at admission in combination with Se and CP levels after 24 h allowed a prediction for potential remission, with an area under the curve (AUC) of 87.7% (CI: 75.1%-100.0%). CONCLUSION These data indicate a strong association between temporal changes of the Se and Cu status and the clinical outcome after TSCI. The dynamics observed may reflect an ongoing redistribution of the trace elements in favor of a better anti-inflammatory response and a more successful neurological regeneration.