Impact of Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein in Patients with Hepatitis C Virus-Related Compensated Liver Cirrhosis

We aimed to examine the effect of Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA⁺-M2BP) level on survival comparing with other laboratory liver fibrosis markers in hepatitis C virus (HCV)-related compensated liver cirrhosis (LC) (n = 165). For assessing prognostic performance of continuous fibrosis markers, we adapted time-dependent receiver operating characteristics (ROC) curves for clinical outcome. In time-dependent ROC analysis, annual area under the ROCs (AUROCs) were plotted. We also calculated the total sum of AUROCs in all time-points (TAAT score) in each fibrosis marker. WFA⁺-M2BP value ranged from 0.66 cutoff index (COI) to 19.95 COI (median value, 5.29 COI). Using ROC analysis for survival, the optimal cutoff point for WFA⁺-M2BP was 6.15 COI (AUROC = 0.79348, sensitivity = 80.0%, specificity = 74.78%). The cumulative five-year survival rate in patients with WFA⁺-M2BP ≥ 6.15 COI (n = 69) was 43.99%, while that in patients with WFA⁺-M2BP < 6.15 COI (n = 96) was 88.40% (p < 0.0001). In the multivariate analysis, absence of hepatocellular carcinoma (p = 0.0008), WFA⁺-M2BP < 6.15 COI (p = 0.0132), achievement of sustained virological response (p < 0.0001) and des-γ-carboxy prothrombin < 41 mAU/mL (p = 0.0018) were significant favorable predictors linked to survival. In time-dependent ROC analysis in all cases, WFA⁺-M2BP had the highest TAAT score among liver fibrosis markers. In conclusion, WFA⁺-M2BP can be a useful predictor in HCV-related compensated LC.     

Correlations of Hepatic Hemodynamics,Liver Function,and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.     

Thiacalixarenes with Sulfur Functionalities at Lower Rim: Heavy Metal Ion Binding in Solution and 2D-Confined Space

Sulfur-containing groups preorganized on macrocyclic scaffolds are well suited for liquid-phase complexation of soft metal ions; however, their binding potential was not extensively studied at the air–water interface, and the effect of thioether topology on metal ion binding mechanisms under various conditions was not considered. Herein, we report the interface receptor characteristics of topologically varied thiacalixarene thioethers (linear bis-(methylthio)ethoxy derivative L², O₂S₂-thiacrown-ether L³, and O₂S₂-bridged thiacalixtube L⁴). The study was conducted in bulk liquid phase and Langmuir monolayers. For all compounds, the highest liquid-phase extraction selectivity was revealed for Ag⁺ and Hg²⁺ ions vs. other soft metal ions. In thioether L² and thiacalixtube L⁴, metal ion binding was evidenced by a blue shift of the band at 303 nm (for Ag⁺ species) and the appearance of ligand-to-metal charge transfer bands at 330–340 nm (for Hg²⁺ species). Theoretical calculations for thioether L² and its Ag and Hg complexes are consistent with experimental data of UV/Vis, nuclear magnetic resonance (NMR) spectroscopy, and single-crystal X-ray diffractometry of Ag–thioether L² complexes and Hg–thiacalixtube L⁴ complex for the case of coordination around the metal center involving two alkyl sulfide groups (Hg²⁺) or sulfur atoms on the lower rim and bridging unit (Ag⁺). In thiacrown L³, Ag and Hg binding by alkyl sulfide groups was suggested from changes in NMR spectra upon the addition of corresponding salts. In spite of the low ability of the thioethers to form stable Langmuir monolayers on deionized water, one might argue that the monolayers significantly expand in the presence of Hg salts in the water subphase. Hg²⁺ ion uptake by the Langmuir–Blodgett (LB) films of ligand L³ was proved by X-ray photoelectron spectroscopy (XPS). Together, these results demonstrate the potential of sulfide groups on the calixarene platform as receptor unit towards Hg²⁺ ions, which could be useful in the development of Hg²⁺-selective water purification systems or thin-film sensor devices.     

Studies on promising cell performance with H2SO4 as the catholyte for electrogeneration of Ag2+ from Ag+ in HNO3 anolyte in mediated electrochemical oxidation process

Electrochemical performance of a divided cell with electrogeneration of Ag²⁺ from Ag⁺ in 6 M HNO₃ anolyte has been studied with 6 M HNO₃ or 3 M H₂SO₄ as the catholyte. This work arose because in mediated electrochemical oxidation (MEO) processes with Ag(II)/Ag(I) redox mediator, HNO₃ is generally used as catholyte, which, however, produces NO _x gases in the cathode compartment. The performance of the cell with 6 M HNO₃ or 3 M H₂SO₄ as the catholyte has been compared in terms of (i) the acid concentration in the cathode compartment, (ii) the Ag⁺ to Ag²⁺ conversion efficiency in the anolyte, (iii) the migration of Ag⁺ from anolyte to catholyte across the membrane separator, and (iv) the cell voltage. Studies with various concentrations of H₂SO₄ catholyte have been carried-out, and the cathode surfaces have been analyzed by SEM and EDXA; similarly, the precipitated material collected in the cathode compartment at higher H₂SO₄ concentrations has been analyzed by XRD to understand the underlying processes. The various beneficial effects in using H₂SO₄ as catholyte have been presented. A simple cathode surface renewal method relatively free from Ag deposit has been suggested.     

Deficiency in Inactive Rhomboid Protein2 (iRhom2) Alleviates Alcoholic Liver Fibrosis by Suppressing Inflammation and Oxidative Stress

Chronic alcohol exposure can lead to liver pathology relating to inflammation and oxidative stress, which are two of the major factors in the incidence of liver fibrosis and even liver cancer. The underlying molecular mechanisms regarding hepatic lesions associated with alcohol are not fully understood. Considering that the recently identified iRhom2 is a key pathogenic mediator of inflammation, we performed in vitro and in vivo experiments to explore its regulatory role in alcohol-induced liver fibrosis. We found that iRhom2 knockout significantly inhibited alcohol-induced inflammatory responses in vitro, including elevated expressions of inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α) and genes associated with inflammatory signaling pathways, such as TACE (tumor necrosis factor-alpha converting enzyme), TNFR1 (tumor necrosis factor receptor 1), and TNFR2, as well as the activation of NF-κB. The in vivo results confirmed that long-term alcohol exposure leads to hepatocyte damage and fibrous accumulation. In this pathological process, the expression of iRhom2 is promoted to activate the TACE/NF-κB signaling pathway, leading to inflammatory responses. Furthermore, the deletion of iRhom2 blocks the TACE/NF-κB signaling pathway and reduces liver damage and fibrosis caused by alcohol. Additionally, the activation of the JNK/Nrf2/HO-1 signaling pathway caused by alcohol exposure was also noted in vitro and in vivo. In the same way, knockout or deleting iRhom2 blocked the JNK/Nrf2/HO-1 signaling pathway to regulate the oxidative stress. Therefore, we contend that iRhom2 is a key regulator that promotes inflammatory responses and regulates oxidative stress in alcoholic liver fibrosis lesions. We posit that iRhom2 is potentially a new therapeutic target for alcoholic liver fibrosis.     

Electrochemical Characteristics of Lithium Transition-Metal Oxide as an Anode Material in a Lithium Secondary Battery

Lithium transition-metal oxides (LiTMOs) such as LiCoO₂ and LiMn₂O₄ were investigated for their use as anode material for the lithium secondary battery. Ni|Li⁰|LiPF₆(lM, EC + DEC (1 : l))|LiTMO|Cu cell was fabricated and its electrochemical properties were examined. LiCoO₂ and LiMn₂O₄ showed fairly good characteristics as anode material as well as cathode material. At the 1st cathodic process, LiCoO₂ had a potential plateau at 1.4 V on open circuit potential line, but LiMn₂O₄ had two ambiguous potential plateaus between 0.6 and 0.1 V. The specific resistance of Li|LiCoO₂ cell was 8 ohm-g, but that of Li|LiMn{si2}O{si4} cell decreased gradually while the reaction proceeded. The specific capacities of Li|LiCoO² and Li|LiMn²O⁴ cells at the 1st discharge were about 300 mAh/g. Capacity retention of Li| LiMn₂O⁴ cell during charge-discharge cycling was higher than that of Li|LiCoO² cell.     

Rufinamide,a Triazole-Derived Antiepileptic Drug,Stimulates Ca2+-Activated K+ Currents While Inhibiting Voltage-Gated Na+ Currents

Rufinamide (RFM) is a clinically utilized antiepileptic drug that, as a triazole derivative, has a unique structure. The extent to which this drug affects membrane ionic currents remains incompletely understood. With the aid of patch clamp technology, we investigated the effects of RFM on the amplitude, gating, and hysteresis of ionic currents from pituitary GH₃ lactotrophs. RFM increased the amplitude of Ca²⁺-activated K⁺ currents (I_K(Ca)) in pituitary GH₃ lactotrophs, and the increase was attenuated by the further addition of iberiotoxin or paxilline. The addition of RFM to the cytosolic surface of the detached patch of membrane resulted in the enhanced activity of large-conductance Ca²⁺-activated K⁺ channels (BK_Ca channels), and paxilline reversed this activity. RFM increased the strength of the hysteresis exhibited by the BK_Ca channels and induced by an inverted isosceles-triangular ramp pulse. The peak and late voltage-gated Na⁺ current (I_Na) evoked by rapid step depolarizations were differentially suppressed by RFM. The molecular docking approach suggested that RFM bound to the intracellular domain of K_Ca1.1 channels with amino acid residues, thereby functionally affecting BK_Ca channels’ activity. This study is the first to present evidence that, in addition to inhibiting the I_Na, RFM effectively modifies the I_K(Ca), which suggests that it has an impact on neuronal function and excitability.     

Highly Selective and Efficient Membrane Transport of Copper as Cu(SCN)2− 4 Ion Using K+-Dicyclohexyl-18-crown-6 as Carrier

Abstract

Potassium-Dicyclohexyl-18-Crown-6 Complex Was Used As A Highly Efficient Carrier For The Uphill Transport Of Copper As Cu(SCN)^2? ₄ Complex Ion Through A Chloroform Bulk Liquid Membrane. By Using Histidine As A Metal Ion Acceptor In The Receiving Phase At The Optimum Ph Of 7.4, The Amount Of Copper Transported Across The Liquid Membrane After 2 Hours Was 90.2 ± 1.0%. The Selectivity And Efficiency Of Copper Transport From Aqueous Solutions Containing Equimolar Mixtures Of Ag⁺, Cd²⁺, Zn²⁺, Ni²⁺, Fe²⁺, Co²⁺, Pb²⁺, Mn²⁺, Fe³⁺, Bi³⁺, And Cr³⁺ Ions Were Investigated. In The Presence Of Pyrophosphate As A Suitable Masking Agent In The Source Phase, The Interfering Effects Of Co²⁺, Zn²⁺, Pb²⁺, And Cd²⁺ Ions Were Completely Eliminated.     

The promotional effect of Cr on catalytic activity of Pt/ZSM-35 for H2-SCR in excess oxygen

Selective catalytic reduction of NO by hydrogen was studied over Cr modified Pt/ZSM-35 catalysts. The preparation process greatly influenced catalytic activity and sample prepared by co-impregnation method exhibits the best activity. In situ DRIFT studies revealed that on Pt–Cr/ZSM-35, (1) new Pt-NO^δ+ and NO species adsorbed on Pt were detected upon NO + O₂ adsorption; (2) much more ammonia species were formed under reaction condition. Cr addition not only enhanced the adsorption of NO_x but also promoted the formation of surface NH₄⁺ species, which should be the origin of promotional effect of Cr on Pt/ZSM-35 for H₂-SCR reaction.     

Differential Regulation of Interferon Signaling Pathways in CD4+ T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype

In the era of personalized medicine, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as asthma phenotypes including obesity-associated asthma, are urgently needed. Peripheral blood was drawn from 10 obese, non-atopic asthmatic adults with a high body mass index (BMI; 36.67 ± 6.90); 10 non-obese, non-atopic asthmatic adults with normal BMI (23.88 ± 2.73); and 10 healthy controls with normal BMI (23.62 ± 3.74). All asthmatic patients were considered to represent a low type-2 asthma phenotype according to selective clinical parameters. RNA sequencing (RNA-Seq) was conducted on peripheral blood CD4⁺ T cells. Thousands of differentially expressed genes were identified in both asthma groups compared with heathy controls. The expression of interferon (IFN)-stimulated genes associated with IFN-related signaling pathways was specifically affected in obese asthmatics, while the gap junction and G protein-coupled receptor (GPCR) ligand binding pathways were enriched in both asthma groups. Furthermore, obesity gene markers were also upregulated in CD4⁺ T cells from obese asthmatics compared with the two other groups. Additionally, the enriched genes of the three abovementioned pathways showed a unique correlation pattern with various laboratory and clinical parameters. The specific activation of IFN-related signaling and viral infection pathways might provide a novel view of the molecular mechanisms associated with the development of the low type-2 obesity-associated asthma phenotype, which is a step ahead in the development of new stratified therapeutic approaches.     

In Silico Drug Repositioning to Target the SARS-CoV-2 Main Protease as Covalent Inhibitors Employing a Combined Structure-Based Virtual Screening Strategy of Pharmacophore Models and Covalent Docking

The epidemic caused by the SARS-CoV-2 coronavirus, which has spread rapidly throughout the world, requires urgent and effective treatments considering that the appearance of viral variants limits the efficacy of vaccines. The main protease of SARS-CoV-2 (M^pro) is a highly conserved cysteine proteinase, fundamental for the replication of the coronavirus and with a specific cleavage mechanism that positions it as an attractive therapeutic target for the proposal of irreversible inhibitors. A structure-based strategy combining 3D pharmacophoric modeling, virtual screening, and covalent docking was employed to identify the interactions required for molecular recognition, as well as the spatial orientation of the electrophilic warhead, of various drugs, to achieve a covalent interaction with Cys145 of M^pro. The virtual screening on the structure-based pharmacophoric map of the SARS-CoV-2 M^pro in complex with an inhibitor N3 (reference compound) provided high efficiency by identifying 53 drugs (FDA and DrugBank databases) with probabilities of covalent binding, including N3 (Michael acceptor) and others with a variety of electrophilic warheads. Adding the energy contributions of affinity for non-covalent and covalent docking, 16 promising drugs were obtained. Our findings suggest that the FDA-approved drugs Vaborbactam, Cimetidine, Ixazomib, Scopolamine, and Bicalutamide, as well as the other investigational peptide-like drugs (DB04234, DB03456, DB07224, DB7252, and CMX-2043) are potential covalent inhibitors of SARS-CoV-2 M^pro.     

Biologically Fixed N2 as a Source for N2O Production in a Grass–clover Mixture, Measured by 15N2

The contribution of biologically fixed dinitrogen (N₂) to the nitrous oxide (N₂O) production in grasslands is unknown. To assess the contribution of recently fixed N₂ as a source of N₂O and the transfer of fixed N from clover to companion grass, mixtures of white clover and perennial ryegrass were incubated for 14 days in a growth cabinet with a ¹⁵N₂-enriched atmosphere (0.4 atom% excess). Immediately after labelling, half of the grass–clover pots were sampled for N₂ fixation determination, whereas the remaining half were examined for emission of ¹⁵N labelled N₂O for another 8 days using a static chamber method. Biological N₂ fixation measured in grass–clover shoots and roots as well as in soil constituted 342, 38 and 67 mg N m⁻² d⁻¹ at 16, 26 and 36 weeks after emergence, respectively. The drop in N₂ fixation was most likely due to a severe aphid attack on the clover component. Transfer of recently fixed N from clover to companion grass was detected at 26 and 36 weeks after emergence and amounted to 0.7 ± 0.1 mg N m⁻² d⁻¹, which represented 1.7 ± 0.3% of the N accumulated in grass shoots during the labelling period. Total N₂O emission was 91, 416 and 259 μg N₂O–N m⁻² d⁻¹ at 16, 26 and 36 weeks after emergence, respectively. Only 3.2 ± 0.5 ppm of the recently fixed N₂ was emitted as N₂O on a daily basis, which accounted for 2.1 ± 0.5% of the total N₂O–N emission. Thus, recently fixed N released via easily degradable clover residues appears to be a minor source of N₂O. An erratum to this article is available at .     

Abnormal Ca2+ Signals in Reactive Astrocytes as a Common Cause of Brain Diseases

In pathological brain conditions, glial cells become reactive and show a variety of responses. We examined Ca²⁺ signals in pathological brains and found that reactive astrocytes share abnormal Ca²⁺ signals, even in different types of diseases. In a neuropathic pain model, astrocytes in the primary sensory cortex became reactive and showed frequent Ca²⁺ signals, resulting in the production of synaptogenic molecules, which led to misconnections of tactile and pain networks in the sensory cortex, thus causing neuropathic pain. In an epileptogenic model, hippocampal astrocytes also became reactive and showed frequent Ca²⁺ signals. In an Alexander disease (AxD) model, hGFAP-R239H knock-in mice showed accumulation of Rosenthal fibers, a typical pathological marker of AxD, and excessively large Ca²⁺ signals. Because the abnormal astrocytic Ca²⁺ signals observed in the above three disease models are dependent on type II inositol 1,4,5-trisphosphate receptors (IP₃RII), we reanalyzed these pathological events using IP₃RII-deficient mice and found that all abnormal Ca²⁺ signals and pathologies were markedly reduced. These findings indicate that abnormal Ca²⁺ signaling is not only a consequence but may also be greatly involved in the cause of these diseases. Abnormal Ca²⁺ signals in reactive astrocytes may represent an underlying pathology common to multiple diseases.     

Genome-Wide Identification and Expression Analysis of AMT and NRT Gene Family in Pecan (Carya illinoinensis) Seedlings Revealed a Preference for NH4+-N

Nitrogen (N) is a major limiting factor for plant growth and crop production. The use of N fertilizer in forestry production is increasing each year, but the loss is substantial. Mastering the regulatory mechanisms of N uptake and transport is a key way to improve plant nitrogen use efficiency (NUE). However, this has rarely been studied in pecans. In this study, 10 AMT and 69 NRT gene family members were identified and systematically analyzed from the whole pecan genome using a bioinformatics approach, and the expression patterns of AMT and NRT genes and the uptake characteristics of NH₄⁺ and NO₃⁻ in pecan were analyzed by aeroponic cultivation at varying NH₄⁺/NO₃⁻ ratios (0/0, 0/100,25/75, 50/50, 75/25,100/0 as CK, T1, T2, T3, T4, and T5). The results showed that gene duplication was the main reason for the amplification of the AMT and NRT gene families in pecan, both of which experienced purifying selection. Based on qRT-PCR results, CiAMTs were primarily expressed in roots, and CiNRTs were majorly expressed in leaves, which were consistent with the distribution of pecan NH₄⁺ and NO₃⁻ concentrations in the organs. The expression levels of CiAMTs and CiNRTs were mainly significantly upregulated under N deficiency and T4 treatment. Meanwhile, T4 treatment significantly increased the NH₄⁺, NO₃⁻, and NO₂⁻ concentrations as well as the Vmax and Km values of NH₄⁺ and NO₃⁻ in pecans, and Vmax/Km indicated that pecan seedlings preferred to absorb NH₄⁺. In summary, considering the single N source of T5, we suggested that the NH₄⁺/NO₃⁻ ratio of 75:25 was more beneficial to improve the NUE of pecan, thus increasing pecan yield, which provides a theoretical basis for promoting the scale development of pecan and provides a basis for further identification of the functions of AMT and NRT genes in the N uptake and transport process of pecan.     

NPA-Cu2+ Complex as a Fluorescent Sensing Platform for the Selective and Sensitive Detection of Glyphosate

Glyphosate is a highly effective, low-toxicity, broad-spectrum herbicide, which is extensively used in global agriculture to control weeds and vegetation. However, glyphosate has become a potential threat to human and ecosystem because of its excessive usage and its bio-concentration in soil and water. Herein, a novel turn-on fluorescent probe, N-n-butyl-4-(3-pyridin)ylmethylidenehydrazine-1,8-naphthalimide (NPA), is proposed. It efficiently detected Cu²⁺ within the limit of detection (LOD) of 0.21 μM and displayed a dramatic turn-off fluorescence response in CH₃CN. NPA-Cu²⁺ complex was employed to selectively and sensitively monitor glyphosate concentrations in real samples accompanied by a fluorescence turn-on mode. A good linear relationship between NPA and Cu²⁺ of glyphosate was found in the range of 10–100 μM with an LOD of 1.87 μM. Glyphosate exhibited a stronger chelation with Cu²⁺ than NPA and the system released free NPA through competitive coordination. The proposed method demonstrates great potential in quantitatively detecting glyphosate in tap water, local water from Songhua River, soil, rice, millet, maize, soybean, mung bean, and milk with mild conditions, and is a simple procedure with obvious consequences and no need for large instruments or pretreatment.     

Sn-containing layered double hydroxides as precursors for nano-sized ZnO/SnO2 photocatalysts

Sn⁴⁺-containing LDH was prepared using the co-precipitation method at constant pH, and characterized using X-ray diffraction, UV–vis diffuse reflectance spectroscopy and TG/DTG methods. The obtained product was further exposed to different thermal treatments in order to obtain nano-sized coupled ZnO/SnO₂ systems with enhanced photocatalytic performances than the ones obtained by mixing the two semiconductor oxides. The formation of a well-defined ZnO/SnO₂ system and the crystallite size, fully investigated using XRD, micro-Raman scattering and UV–vis DR techniques, were found to be influenced by the nature of the precursors and the calcination temperature. The photocatalytic activity of the ZnO/SnO₂ systems, evaluated for the photodegradation of methyl orange (MO) dye, was studied as a function of the initial pH, catalyst loading and the calcination temperature. The metal dispersion supplied by layered structures proved to be an advantage when preparing coupled ZnO/SnO₂ systems, the photocatalytic activity being 2.3 times higher comparing with the physical mixtures performances. The maximum photocatalytic activity of the coupled ZnO/SnO₂ system having a layered precursor was observed when using neutral pH, at a catalyst loading of 1 g/L calcined at 600 °C for 4 h.     

Binding of Citrate-Fe3+ to Plastic Culture Dishes,an Artefact Useful as a Simple Technique to Screen for New Iron Chelators

NaCT mediates citrate uptake in the liver cell line HepG2. When these cells were exposed to iron (Fe³⁺), citrate uptake/binding as monitored by the association of [¹⁴C]-citrate with cells increased. However, there was no change in NaCT expression and function, indicating that NaCT was not responsible for this Fe³⁺-induced citrate uptake/binding. Interestingly however, the process exhibited substrate selectivity and saturability as if the process was mediated by a transporter. Notwithstanding these features, subsequent studies demonstrated that the iron-induced citrate uptake/binding did not involve citrate entry into cells; instead, the increase was due to the formation of citrate-Fe³⁺ chelate that adsorbed to the cell surface. Surprisingly, the same phenomenon was observed in culture wells without HepG2 cells, indicating the adsorption of the citrate-Fe³⁺ chelate to the plastic surface of culture wells. We used this interesting phenomenon as a simple screening technique for new iron chelators with the logic that if another iron chelator is present in the assay system, it would compete with citrate for binding to Fe³⁺ and prevent the formation and adsorption of citrate-Fe³⁺ to the culture well. This technique was validated with the known iron chelators deferiprone and deferoxamine, and with the bacterial siderophore 2,3-dihydroxybenzoic acid and the catechol carbidopa.     

MPP+-Induced Changes in Cellular Impedance as a Measure for Organic Cation Transporter (SLC22A1-3) Activity and Inhibition

The organic cation transporters OCT1-3 (SLC22A1-3) facilitate the transport of cationic endo- and xenobiotics and are important mediators of drug distribution and elimination. Their polyspecific nature makes OCTs highly susceptible to drug–drug interactions (DDIs). Currently, screening of OCT inhibitors depends on uptake assays that require labeled substrates to detect transport activity. However, these uptake assays have several limitations. Hence, there is a need to develop novel assays to study OCT activity in a physiological relevant environment without the need to label the substrate. Here, a label-free impedance-based transport assay is established that detects OCT-mediated transport activity and inhibition utilizing the neurotoxin MPP⁺. Uptake of MPP⁺ by OCTs induced concentration-dependent changes in cellular impedance that were inhibited by decynium-22, corticosterone, and Tyrosine Kinase inhibitors. OCT-mediated MPP⁺ transport activity and inhibition were quantified on both OCT1-3 overexpressing cells and HeLa cells endogenously expressing OCT3. Moreover, the method presented here is a valuable tool to identify novel inhibitors and potential DDI partners for MPP⁺ transporting solute carrier proteins (SLCs) in general.     

Functionalized magnetic core-shell Fe3O4@SiO2 nanoparticles as selectivity-enhanced chemosensor for Hg(II)

A colorimetric and ‘‘turn-on” fluorescent chemosensor Rho-Fe₃O₄@SiO₂ for Hg²⁺ in which N-(rhodamine-6G)lactam-ethylenediamine (Rho-en) is conjugated with the magnetic core-shell Fe₃O₄@SiO₂ NPs has been strategically designed and synthesized. The final product was characterized by X-ray power diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectra (FTIR) and UV-visible absorption and fluorescence emission. Fluorescence and UV-visible spectra results showed that the resultant multifunctional nanoparticles Rho-Fe₃O₄@SiO₂ exhibited selective ‘turn-on’ type fluorescent enhancements and distinct color changes with Hg²⁺. The selectivity of the Rho-Fe₃O₄@SiO₂ for Hg(II) ion is better than that of the Rho-en in the same conditions. In addition, the presence of magnetic Fe₃O₄ nanoparticles in the sensor Rho-Fe₃O₄@SiO₂ NPs would also facilitate the magnetic separation of the Hg(II)-Rho-Fe₃O₄@SiO₂ from the solution.