Interferon Beta Activity Is Modulated via Binding of Specific S100 Proteins

Interferon-β (IFN-β) is a pleiotropic cytokine used for therapy of multiple sclerosis, which is also effective in suppression of viral and bacterial infections and cancer. Recently, we reported a highly specific interaction between IFN-β and S100P lowering IFN-β cytotoxicity to cancer cells (Int J Biol Macromol. 2020; 143: 633–639). S100P is a member of large family of multifunctional Ca²⁺-binding proteins with cytokine-like activities. To probe selectivity of IFN-β—S100 interaction with respect to S100 proteins, we used surface plasmon resonance spectroscopy, chemical crosslinking, and crystal violet assay. Among the thirteen S100 proteins studied S100A1, S100A4, and S100A6 proteins exhibit strictly Ca²⁺-dependent binding to IFN-β with equilibrium dissociation constants, K_d, of 0.04–1.5 µM for their Ca²⁺-bound homodimeric forms. Calcium depletion abolishes the S100—IFN-β interactions. Monomerization of S100A1/A4/A6 decreases K_d values down to 0.11–1.0 nM. Interferon-α is unable of binding to the S100 proteins studied. S100A1/A4 proteins inhibit IFN-β-induced suppression of MCF-7 cells viability. The revealed direct influence of specific S100 proteins on IFN-β activity uncovers a novel regulatory role of particular S100 proteins, and opens up novel approaches to enhancement of therapeutic efficacy of IFN-β.     

Multilevel Changes in Protein Dynamics upon Complex Formation of the Calcium‐Loaded S100A4 with a Nonmuscle Myosin IIA Tail Fragment

Dysregulation of Ca²⁺‐binding S100 proteins plays important role in various diseases. The asymmetric complex of Ca²⁺‐bound S100A4 with nonmuscle myosin IIA has high stability and highly increased Ca²⁺ affinity. Here we investigated the possible causes of this allosteric effect by NMR spectroscopy. Chemical shift‐based secondary‐structure analysis did not show substantial changes for the complex. Backbone dynamics revealed slow‐timescale local motions in the H1 helices of homodimeric S100A4; these were less pronounced in the complex form and might be accompanied by an increase in dimer stability. Different mobilities in the Ca²⁺‐coordinating EF‐hand sites indicate that they communicate by an allosteric mechanism operating through changes in protein dynamics; this must be responsible for the elevated Ca²⁺ affinity. These multilevel changes in protein dynamics as conformational adaptation allow S100A4 fine‐tuning of its protein–protein interactions inside the cell during Ca²⁺ signaling.     

Effects of added metal ions on the interaction of chitin and partially deacetylated chitin with an azo dye carrying hydroxyl groups

The binding of chrome violet, which is a monoazo dye and involves two hydroxyl groups in the o and o′ positions to an azo group, to chintin and partially decetylated chitin, was examined in the presence of metal ions. Zn²⁺ and Cu²⁺ ions do not perceptively influence the binding affinity of chrome voilet to chitin. In contrast, Co²⁺ ion enhances the binding and Ni²⁺ ion suppresses it. In the lower free dye concentrations the dye uptake by partially deceteylated chitin was tremendously enhanced by adding. Co²⁺ ion in the buffer solution of pH 5. The dye uptake by the polymer was considerably increased by the addition of Cu²⁺ ion at pH 5 and became much larger at pH 6. The amount corresponded to that in the presence of Co²⁺ ion. To investigate further the action of added metal ions, a cobalt- or a chrome–complex dye was prepared, and the binding properties for the polymers were compared with those of chrome violet in the presence of Co²⁺ and Cu²⁺ ions. Some possible mechanisms for the enhancement of chrome violet binding by the addition of Co²⁺ and Cu²⁺ ions are described. © 1995 John Wiley & Sons, Inc.     

Hydrothermal Synthesis of Mn–Fe Nano Oxides and Their Composite for Removal of Zn<Superscript>2+</Superscript>, Ni<Superscript>2+</Superscript> and Co<Superscript>2+</Superscript> from Simulated Radioactive Waste

A study on the sorption of Zn²⁺, Ni²⁺ and Co²⁺ onto mixed oxide of Mn and Fe obtained at different hydrothermal conditions and its organic hybrid film modified with polyacrylamide (Mn–Fe oxide/PAM) has been examined. The characterization of inorganic oxides and its composite samples were performed using XRD, SEM, FTIR, XRF and DTA-TGA techniques. The percent sorption of Zn²⁺, Ni²⁺ and Co²⁺ on Mn–Fe oxide at pH 4.5 was 97, 11.85 and 10 % respectively with selectivity order Zn²⁺ ? Ni²⁺ > Co²⁺. The sorption value of Zn²⁺ at pH 4.5 onto Fe–Mn oxide reached nearly the same value of Zn²⁺ onto its composite. So, the new compound of Fe–Mn oxide has promising uses for separation of zinc ions while its composite can be used for removal all of these cations.     

Kinetics of the sorption of heavy-metal ions by a sorbent obtained from boric acid production waste

The results of studies of kinetic regularities of sorption of heavy-metals ions (Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, and Mn²⁺) by a sorbent based on calcium hydrosilicate (hereinafter referred to as silicate sorbent) produced from manmade waste formed during the processing of the boron-containing mineral raw materials (boron–gypsum) have been presented.     

IFCC recommendation on sampling,transport and storage for the determination of the concentration of ionized calcium in whole blood,plasma and serum

The substance concentration of ionized calcium (c _Ca²⁺) in blood, plasma or serum preanalytically may be affected by pH changes of the sample, calcium binding by heparin, and dilution by the anticoagulant solution.pH changes in whole blood can be minimized by anaerobic sampling to avoid loss of Co₂, by measuring as soon as possible, or by storing the sample in iced water to avoid lactic acid formation. c_Ca ²⁺ and pH should be determined simultaneously.Plasma or serum: If centrifuged in a closed tube, and measured immediately, the pH of the sample will be close to the original value. If a delay has occurred between centrifugation and the measurement, causing substantial loss of Co₂, equilibration of the sample with a gas mixture corresponding to pCO2= 5.3 kPa prior to the measurement is recommended. Conversion of the measured values to c_Ca ²⁺ (7.4) is only valid if the pH is in the range 7.2-7.6.Ca²⁺ binding by heparin can be minimized by using either of the following:(1) A final concentration of sodium or lithium heparinate of 15 IU/ml blood or less(2) Calcium titrated heparin with a final concentration of less than 50 IU/ml blood.Dilution effect can be avoided by use of dry heparin in capillaries or syringes. When heparin solutions are used, errors due to dilution or calcium binding can be reduced by using syringes with a heparin solution containing free calcium ions corresponding to the mean concentration of ionized calcium in normal plasma.Conditions for blood collection, storage, and transport to avoid preanalytical errors are described in this paper.     

Catalytic Ozonation of Citric Acid by Metallic Ions in Aqueous Solution

Ozonation of citric acid in water catalyzed by different ions from the first row of transition metals (Mn²⁺, Co²⁺, Ti⁴⁺, Fe²⁺, Cu²⁺, Ni²⁺ and Zn²⁺) was investigated at room temperature. The results showed that at pH=2, where the decomposition of citric acid is negligible by only ozone, the following order of efficiency of metallic ions for the decomposition of citric acid by ozone, and also for the TOC removal, was obtained: Mn²⁺ > Co²⁺ > Ti⁴⁺ > Fe²⁺. Cu²⁺, Ni²⁺ and Zn²⁺ showed negligible efficiency under the same experimental conditions. At pH=5.5, Mn²⁺ and Co²⁺ showed slightly higher efficiency than at pH=2 while Ti⁴⁺ and Fe²⁺ showed insignificant effect at this pH value. On the other hand, at pH=7 the investigated catalysts showed no obvious catalytic efficiency for the decomposition of citric acid by ozone.     

Competitive binding of divalent cations to poly(α-hydroxyacrylic acid)

The competitive binding of divalent cations (Mg²⁺, Ca²⁺, Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺ and Zn²⁺) on poly(α-hydroxyacrylic acid) (PHA) and poly(acrylic acid) (PAA) was investigated by equilibrium dialysis. In the Mg/Ca mixed system, binding selectivity for Ca²⁺ over Mg²⁺ was significantly higher in PHA than in PAA; this was attributed to coordination of α-OH groups on PHA to Ca²⁺. The binding ability and selectivity for the transition metal cations were almost the same for PHA and PAA at neutral pH, while PHA maintained appreciably higher degrees of binding than PAA in acidic solutions (pH about 3). This cation binding ability of PHA was ascribed to the lower pK_a value in the relevant pH region. © 1998 SCI.     

Interferon-β Activity Is Affected by S100B Protein

Interferon-β (IFN-β) is a pleiotropic cytokine secreted in response to various pathological conditions and is clinically used for therapy of multiple sclerosis. Its application for treatment of cancer, infections and pulmonary diseases is limited by incomplete understanding of regulatory mechanisms of its functioning. Recently, we reported that IFN-β activity is affected by interactions with S100A1, S100A4, S100A6, and S100P proteins, which are members of the S100 protein family of multifunctional Ca²⁺-binding proteins possessing cytokine-like activities (Int J Mol Sci. 2020;21(24):9473). Here we show that IFN-β interacts with one more representative of the S100 protein family, the S100B protein, involved in numerous oncological and neurological diseases. The use of chemical crosslinking, intrinsic fluorescence, and surface plasmon resonance spectroscopy revealed IFN-β binding to Ca²⁺-loaded dimeric and monomeric forms of the S100B protein. Calcium depletion blocks the S100B–IFN-β interaction. S100B monomerization increases its affinity to IFN-β by 2.7 orders of magnitude (equilibrium dissociation constant of the complex reaches 47 pM). Crystal violet assay demonstrated that combined application of IFN-β and S100B (5–25 nM) eliminates their inhibitory effects on MCF-7 cell viability. Bioinformatics analysis showed that the direct modulation of IFN-β activity by the S100B protein described here could be relevant to progression of multiple oncological and neurological diseases.     

Studies of selective adsorption resins. XXV. Preparation of macroreticular chelating resins containing aminomethylphosphonic acid groups from methyl methacrylate/divinylbenzene copolymer beads and their adsorption capacity

Macroreticular chelating resins containing aminomethylphosphonic acid groups were prepared by reaction of methyl methacrylate/divinylbenzene copolymer beads with triethylenetetramine, followed by the reaction of the products with phosphorous acid and formaline. The adsorption capacities of this resin for Cu²⁺, Pb²⁺, Zn²⁺, Ni²⁺, Co²⁺, Ca²⁺, and Mg²⁺ were determined at various pH values. The order of chelate stability for the resin was Cu²⁺ > Pb²⁺ > Zn²⁺ > Ni²⁺ > Co²⁺ > Ca²⁺ > Mg²⁺. Copper, nickel, zinc, calcium, and magnesium ions can be eluted with 1 mol dm^?3 hydrochloric acid. The proposed resin appears to be useful for the removal of Ca²⁺ and Mg²⁺ from salt solution.     

Equilibrium,kinetic and isotherm of some metal ion biosorption

Trichoderma reesei was used as a biosorbent for the removal of Co²⁺, Cu²⁺, Ni²⁺, Pb²⁺ and Zn²⁺ ions. The influence of factors such as pH, mass of biomass, contact time and temperature on biosorption efficiency was optimized. To calculate the isotherm parameters for the biosorption of Co²⁺, Cu²⁺, Ni²⁺, Pb²⁺ and Zn²⁺ ions at optimized conditions, the experimental equilibrium data were fitted to Langmuir and Freundlich models. The calculated thermodynamic parameters, ΔG°, ΔH° and ΔS° showed that the biosorption of Co²⁺, Cu²⁺, Ni²⁺, Pb²⁺ and Zn²⁺ ions onto T. reesei biomass was feasible, spontaneous and endothermic at the optimized conditions. The results of kinetic analysis showed that the biosorption of the selected metal ions onto T. reesei biomass obeys pseudo second order kinetics.     

Role of S100A8/A9 for Cytokine Secretion,Revealed in Neutrophils Derived from ER-Hoxb8 Progenitors

S100A9, a Ca²⁺-binding protein, is tightly associated to neutrophil pro-inflammatory functions when forming a heterodimer with its S100A8 partner. Upon secretion into the extracellular environment, these proteins behave like damage-associated molecular pattern molecules, which actively participate in the amplification of the inflammation process by recruitment and activation of pro-inflammatory cells. Intracellular functions have also been attributed to the S100A8/A9 complex, notably its ability to regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. However, the complete functional spectrum of S100A8/A9 at the intracellular level is far from being understood. In this context, we here investigated the possibility that the absence of intracellular S100A8/A9 is involved in cytokine secretion. To overcome the difficulty of genetically modifying neutrophils, we used murine neutrophils derived from wild-type and S100A9^−/− Hoxb8 immortalized myeloid progenitors. After confirming that differentiated Hoxb8 neutrophil-like cells are a suitable model to study neutrophil functions, our data show that absence of S100A8/A9 led to a dysregulation of cytokine secretion after lipopolysaccharide (LPS) stimulation. Furthermore, we demonstrate that S100A8/A9-induced cytokine secretion was regulated by the nuclear factor kappa B (NF-κB) pathway. These results were confirmed in human differentiated HL-60 cells, in which S100A9 was inhibited by shRNAs. Finally, our results indicate that the degranulation process could be involved in the regulation of cytokine secretion by S100A8/A9.     

Antibody purification from human plasma by metal‐chelated affinity membranes

The aim of this study is to investigate in detail the feasibility of poly(2‐hydroxyethyl methacrylate‐N‐methacryloyl‐(L )‐histidine methyl ester), PHEMAH membranes for purification of immunoglobulin G (IgG) from human plasma. PHEMAH membranes were prepared by photo‐polymerization technique. Then, Zn²⁺, Ni²⁺, Co²⁺, and Cu²⁺ ions were chelated directly on the PHEMAH membranes. Elemental analysis assay was performed to determine the nitrogen content and polymerized MAH was calculated as 168.5 μmol/g. The nonspecific IgG adsorption onto the plain PHEMA membranes was negligible (about 0.25 mg/mL). A remarkable increase in the IgG adsorption capacities were achieved from human plasma with PHEMAH membranes (up to 68.4 mg/mL). Further increase was observed with the metal‐chelated PHEMAH membranes (up to 118 mg/mL). The metal‐chelate affinity membranes allowed the one‐step separation of IgG from human plasma. The binding range of metal ions for surface histidines from human plasma followed the order: Cu²⁺ > Ni²⁺ > Zn²⁺ > Co²⁺. Adsorbed IgG was eluted using 250 mM EDTA with a purity of 94.1%. IgG molecules could be repeatedly adsorbed and eluted with the metal‐chelated PHEMAH membranes without noticeable loss in their IgG adsorption capacity. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Competitive removal of nickel (II), cobalt (II), and zinc (II) ions from aqueous solutions by starch‐graft‐acrylic acid copolymers

Graft copolymerization of acrylic acid (AA) onto starch was carried out with ceric ammonium nitrate as initiator under nitrogen atmosphere. The grafting percentages (GP%) of starch‐graft‐acrylic acid (St‐g‐AA) copolymers were determined. The effect of GP% of St‐g‐AA copolymers on the competitive removal of Co²⁺, Ni²⁺, Zn²⁺ ions from aqueous solution was investigated at different pH (2, 4, 6). The concentrations of each ion in aqueous solution 5 mmol/L. Effects of various parameters such as treatment time, initial pH of the solution and grafting percentage of starch graft copolymers were investigated. Metal ion removal capacities of St‐g‐AA copolymers increased with GP% of the copolymers and pH. The results show that the removal of metal ions followed as given in the order Co²⁺ > Ni²⁺ > Zn²⁺. In this study, metal ion removal capacities were determined by atomic absorption spectrophotometer (AAS). © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Strategies for Therapeutic Amelioration of Aberrant Plasma Zn2+ Handling in Thrombotic Disease: Targeting Fatty Acid/Serum Albumin-Mediated Effects

The initiation, maintenance and regulation of blood coagulation is inexorably linked to the actions of Zn²⁺ in blood plasma. Zn²⁺ interacts with a variety of haemostatic proteins in the bloodstream including fibrinogen, histidine-rich glycoprotein (HRG) and high molecular weight kininogen (HMWK) to regulate haemostasis. The availability of Zn²⁺ to bind such proteins is controlled by human serum albumin (HSA), which binds 70–85% of plasma Zn²⁺ under basal conditions. HSA also binds and transports non-esterified fatty acids (NEFAs). Upon NEFA binding, there is a change in the structure of HSA which leads to a reduction in its affinity for Zn²⁺. This enables other plasma proteins to better compete for binding of Zn²⁺. In diseases where elevated plasma NEFA concentrations are a feature, such as obesity and diabetes, there is a concurrent increase in hypercoagulability. Evidence indicates that NEFA-induced perturbation of Zn²⁺-binding by HSA may contribute to the thrombotic complications frequently observed in these pathophysiological conditions. This review highlights potential interventions, both pharmaceutical and non-pharmaceutical that may be employed to combat this dysregulation. Lifestyle and dietary changes have been shown to reduce plasma NEFA concentrations. Furthermore, drugs that influence NEFA levels such as statins and fibrates may be useful in this context. In severely obese patients, more invasive therapies such as bariatric surgery may be useful. Finally, other potential treatments such as chelation therapies, use of cholesteryl transfer protein (CETP) inhibitors, lipase inhibitors, fatty acid inhibitors and other treatments are highlighted, which with additional research and appropriate clinical trials, could prove useful in the treatment and management of thrombotic disease through amelioration of plasma Zn²⁺ dysregulation in high-risk individuals.     

Chelation ion‐exchange properties of copolymer resin derived from 4‐hydroxyacetophenone,oxamide, and formaldehyde

A copolymer (4‐HAOF) prepared by condensation of 4‐hydroxyacetophenone and oxamide with formaldehyde in the presence of an acid catalyst proved to be a selective chelating ion‐exchange copolymer for certain metals. Chelating ion‐exchange properties of this copolymer were studied for Fe³⁺, Cu²⁺, Ni²⁺, Co²⁺, Zn²⁺, Cd²⁺, Pb²⁺, and Hg²⁺ ions. A batch equilibrium method was employed in the study of the selectivity of metal‐ion uptake involving the measurements of the distribution of a given metal ion between the copolymer sample and a solution containing the metal ion. The study was carried out over a wide pH range and in media of various ionic strengths. The copolymer showed a higher selectivity for Fe³⁺ ions than for Co²⁺, Zn²⁺, Cd²⁺, Pb²⁺, Cu²⁺, Ni²⁺, and Hg²⁺ ions. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 787–790, 2003     

Treatment of industrial wastewater using zeolitite and sepiolite,natural microporous materials

This work investigates the ability of natural microporous materials, such as a zeolite-rich tuff (zeolitite) and a modulated phyllosilicate (sepiolite), to remove heavy-metal ions from simulated inorganic polluted industrial wastewater. Fixed beds of sepiolite and zeolitite were percolated by a solution of Co²⁺, Cu²⁺, Zn²⁺, Cd²⁺, and Pb²⁺ (concentration of each cation, 2 ? 10^?3 N; total concentration, 10^?2 N) and were regenerated with a 2 ? 10^?3 N Na⁺ solution. The order of decreasing affinity was, for sepiolite: Cu²⁺ > Zn²⁺ > Cd²⁺ > Pb²⁺ ? Co²⁺, and, for zeolitite: Pb²⁺ “Cd²⁺ > Cu²⁺ > Zn²⁺ > Co²⁺. After regeneration with Na⁺ solution, a fraction of the retained heavy metals was quickly released by the beds as follows: sepiolite, Co²⁺ ? Pb²⁺ > Cd²⁺ > Zn²⁺ > Cu²⁺; zeolitite, Cd²⁺ > Cu²⁺ ? Zn²⁺ > Co²⁺ > Pb²⁺. XRD and DTA-TGA analyses examined structural changes in the natural and final materials.     

Hierarchical framework of CoZnS as a high-performance electrode material for supercapacitors

Efficient renewable energies are needed to meet the energy demands of modernized civilization. Therefore, this study evaluated composite Co_1-xZn_xS (0.04 ≤ x ≤ 0.34) (CZS-1 to CZS-6) thin film electrodes produced using a chemical growth approach as effective energy storage devices. Systematic integration of Zn²⁺ in the CoS host formed the polycrystalline Co_0.24SZn_0.76 (cubic) phase. The electrochemical measurements revealed a high diffusion rate and low series resistance, resulting in an excellent specific capacitance (C_s) of 1288 F g^?1 at a current density of 2 mA cm^?2 with better rate performance. In addition, the optimal electrode (CZT-5) showed a better power density of 8.86 kW kg^?1 and an energy density of 44.4 Wh kg^?1 with excellent capacitive retention (85% after 5000 cycles). The enhanced performance could stem from the spongy rose flower-like nanostructure with a covered network of polygonic petals. Consequently, the replacement of Co²⁺ with Zn²⁺ also contributed by exchanging the oxidation states of targeted atoms, including Co²⁺, Co³⁺, Zn²⁺, and S^2?. Moreover, surface topographical insight states that crystalline growth of the CZS samples with hillocks and valleys and CZS-5 sample exhibited maximum total roughness.     

Specific S100 Proteins Bind Tumor Necrosis Factor and Inhibit Its Activity

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (K_d) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent K_d values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1–0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatics analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect the efficacy of anti-TNF treatment in various diseases.