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The super-cooling compound icilin stimulates c-Fos and Egr-1 expression and activity involving TRPM8 channel activation, Ca2+ ion influx and activation of the ternary complex factor Elk-1.
Ulrich, M, Wissenbach, U, Thiel, G
Biochemical pharmacology. 2020;:113936
Abstract
The TRPM8 cation channel can be activated by the cooling compound icilin. Recently, we showed that stimulation of TRPM8 channels induces a signaling cascade leading to the activation of the transcription factor AP-1. Additionally, expression of the AP-1 constituent c-Fos has been shown to be induced following TRPM8 stimulation. c-Fos is frequently used as a marker for neuronal activity. Here, we have analyzed the mechanism connecting TRPM8 stimulation and c-Fos expression. Furthermore, we analyzed the expression of the neuronal activity-responsive transcription factor Egr-1 following TRPM8 activation. The results show that icilin-induced stimulation of TRPM8 channels increased c-Fos promoter activity and induced c-Fos expression. Moreover, icilin stimulation increased Egr-1 promoter activity and induced the expression of Egr-1. Pharmacological inhibition of TRPM8 blocked the icilin-induced expression of Egr-1 and c-Fos. An influx of Ca2+ ions into the cells via TRPM8 was necessary to stimulate Egr-1 and c-Fos expression following icilin treatment. Genetic experiments revealed that serum response elements within the Egr-1 and c-Fos promoters are crucial to couple TRPM8 stimulation with enhanced transcription of both the Egr-1 and c-Fos genes. These data were corroborated by experiments showing that TRPM8 stimulation increased the transcriptional activation potential of Elk-1, a SRE binding protein. c-Fos is important for neuronal excitability and survival. Egr-1 plays an important role in synaptic plasticity, consolidation and reconsolidation of long-term memory. Elk-1 may preserve neurons against toxic insults but may also induce depressive behaviour. The fact that TRPM8 stimulation activates the transcription factors c-Fos, Egr-1, and Elk-1 connects TRPM8 signaling with maintaining important brain functions.
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Modern Electrode Technologies for Ion and Molecule Sensing.
Skinner, WS, Ong, KG
Sensors (Basel, Switzerland). 2020;(16)
Abstract
In high concentrations, ionic species can be toxic in the body, catalyzing unwanted bioreactions, inhibiting enzymes, generating free radicals, in addition to having been associated with diseases like Alzheimer's and cancer. Although ionic species are ubiquitous in the environment in trace amounts, high concentrations of these metals are often found within industrial and agricultural waste runoff. Therefore, it remains a global interest to develop technologies capable of quickly and accurately detecting trace levels of ionic species, particularly in aqueous environments that naturally contain other competing/inhibiting ions. Herein, we provide an overview of the technologies that have been developed, including the general theory, design, and benefits/challenges associated with ion-selective electrode technologies (carrier-doped membranes, carbon-based varieties, enzyme inhibition electrodes). Notable variations of these electrodes will be highlighted, and a brief overview of associated electrochemical techniques will be given.
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Influence of the long-term use of oral hygiene products containing stannous ions on the salivary microbiome - a randomized controlled trial.
Anderson, AC, Al-Ahmad, A, Schlueter, N, Frese, C, Hellwig, E, Binder, N
Scientific reports. 2020;(1):9546
Abstract
Oral hygiene products containing tin are suitable to prevent erosive tooth wear, yet effects on the oral microbiota are not known yet. Therefore, this study determined the salivary microbiome of 16 participants using products with stannous ions for three years (TG) compared with a control group (CG) to assess their influence on the microbiota. Participants were included in a randomized controlled clinical trial (RCT) with biannual visits. Illumina Miseq sequencing revealed as most abundant genera: Streptococcus (TG 14.3%; CG 13.0%), Veillonella (TG 11.3%; CG 10.9%), Prevotella (TG 7.0%; CG 9.8%), Haemophilus (TG 6.6%; CG 7.2%), Porphyromonas (TG 5.9%, CG 5.1%), Leptotrichia (TG 5.8%; CG 4.9%), Actinomyces (TG 4.0%; CG 4.6%) and Neisseria (TG 5.4%; CG 4.2%). Beta-Diversity was not significantly different between groups at both time points, although significant differences between groups were found for certain taxa after three years. The genus Prevotella was found in higher abundance in CG whereas Neisseria and Granulicatella, health-associated taxa, were found more abundantly in TG. Salivary microbiota after three years reflected a composition associated with oral health, hence continual use as a preventive measure for dental erosion can be considered safe and benefitting oral health for patients with a high risk of erosion.
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Highly selective sensor for the detection of Hg2+ ions using homocysteine functionalised quartz crystal microbalance with cross-linked pyridinedicarboxylic acid.
Rotake, DR, Kumar, A, Darji, AD, Singh, J
IET nanobiotechnology. 2020;(7):563-573
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Abstract
This study reports an insightful portable vector network analyser (VNA)-based measurement technique for quick and selective detection of Hg2+ ions in nanomolar (nM) range using homocysteine (HCys)-functionalised quartz-crystal-microbalance (QCM) with cross-linked-pyridinedicarboxylic acid (PDCA). The excessive exposure to mercury can cause damage to many human organs, such as the brain, lungs, stomach, and kidneys, etc. Hence, the authors have proposed a portable experimental platform capable of achieving the detection in 20-30 min with a limit of detection (LOD) 0.1 ppb (0.498 nM) and a better dynamic range (0.498 nM-6.74 mM), which perfectly describes its excellent performance over other reported techniques. The detection time for various laboratory-based techniques is generally 12-24 h. The proposed method used the benefits of thin-film, nanoparticles (NPs), and QCM-based technology to overcome the limitation of NPs-based technique and have LOD of 0.1 ppb (0.1 μg/l) for selective Hg2+ ions detection which is many times less than the World Health Organization limit of 6 μg/l. The main advantage of the proposed QCM-based platform is its portability, excellent repeatability, millilitre sample volume requirement, and easy process flow, which makes it suitable as an early warning system for selective detection of mercury ions without any costly measuring instruments.
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ROS and Ions in Cell Signaling during Sexual Plant Reproduction.
Breygina, M, Klimenko, E
International journal of molecular sciences. 2020;(24)
Abstract
Pollen grain is a unique haploid organism characterized by two key physiological processes: activation of metabolism upon exiting dormancy and polar tube growth. In gymnosperms and flowering plants, these processes occur in different time frames and exhibit important features; identification of similarities and differences is still in the active phase. In angiosperms, the growth of male gametophyte is directed and controlled by its microenvironment, while in gymnosperms it is relatively autonomous. Recent reviews have detailed aspects of interaction between angiosperm female tissues and pollen such as interactions between peptides and their receptors; however, accumulated evidence suggests low-molecular communication, in particular, through ion exchange and ROS production, equally important for polar growth as well as for pollen germination. Recently, it became clear that ROS and ionic currents form a single regulatory module, since ROS production and the activity of ion transport systems are closely interrelated and form a feedback loop.
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Molecular Recognition of Zwitterions with Artificial Receptors.
Alfonso, I, Solà, J
Chemistry, an Asian journal. 2020;(7):986-994
Abstract
Many biomolecules exist as internal ion pairs or zwitterions within a biologically relevant pH range. Despite their importance, the molecular recognition of this type of systems is specially challenging due to their strong solvation in aqueous media, and their trend to form folded or self-assembled structures by pairing of charges of different sign. In this Minireview, we will discuss the molecular recognition of zwitterions using non-natural, synthetic receptors. This contribution does not intend to make a full in-depth revision of the existing research in the field, but a personal overview with selected representative examples from the recent literature.
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Free Energy Calculations on the Water-Chain-Assisted and the Dehydration Mechanisms of Transmembrane Ion Permeation.
Guan, X, Wei, DQ, Hu, D
Journal of chemical theory and computation. 2020;(1):700-710
Abstract
Two permeation mechanisms, namely the water-chain-assisted mechanism and the dehydration mechanism, have been proposed for ions through lipid membranes. In previous studies, multiple reaction coordinates and potential of mean force calculations have been applied in studying such complex transmembrane processes of ions. To reduce the expensive computational cost, we develop two new reaction coordinates in our recent work and in this work to study the two permeation mechanisms. An intrinsically one-dimensional free energy calculation method developed in our recent work is successfully employed in these studies: First, one-dimensional umbrella samplings are performed using the two reaction coordinates. Then, bin segmentations are performed along the transition paths in multidimensional phase spaces. Finally, the weighted least-square analysis method (Welsam) is used for free energy analysis. Based on the new reaction coordinates and the one-dimensional free energy calculation method, we systematically study the two transmembrane permeation mechanisms of sodium ion and chloride ion through lipid bilayers with different thicknesses. Our results suggest that the water-chain-assisted mechanism is dominant for cations, whereas the dehydration mechanism is competitive for anions through thick membranes, which is consistent with previous experimental results.
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Ion-Specific Assembly of Strong, Tough, and Stiff Biofibers.
Mittal, N, Benselfelt, T, Ansari, F, Gordeyeva, K, Roth, SV, Wågberg, L, Söderberg, LD
Angewandte Chemie (International ed. in English). 2019;(51):18562-18569
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Abstract
Designing engineering materials with high stiffness and high toughness is challenging as stiff materials tend to be brittle. Many biological materials realize this objective through multiscale (i.e., atomic- to macroscale) mechanisms that are extremely difficult to replicate in synthetic materials. Inspired from the architecture of such biological structures, we here present flow-assisted organization and assembly of renewable native cellulose nanofibrils (CNFs), which yields highly anisotropic biofibers characterized by a unique combination of high strength (1010 MPa), high toughness (62 MJ m-3 ) and high stiffness (57 GPa). We observed that properties of the fibers are primarily governed by specific ion characteristics such as hydration enthalpy and polarizability. A fundamental facet of this study is thus to elucidate the role of specific anion binding following the Hofmeister series on the mechanical properties of wet fibrillar networks, and link this to the differences in properties of dry nanostructured fibers. This knowledge is useful for rational design of nanomaterials and is critical for validation of specific ion effect theories. The bioinspired assembly demonstrated here is relevant example for designing high-performance materials with absolute structural control.
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Hydroxycobalamin catalyzes the oxidation of diethyldithiocarbamate and increases its cytotoxicity independently of copper ions.
Solovieva, ME, Shatalin, YV, Solovyev, VV, Sazonov, AV, Kutyshenko, VP, Akatov, VS
Redox biology. 2019;:28-37
Abstract
It is known that some metals (Cu, Zn, Cd, Au) markedly increase the toxic effect of thiocarbamates. It was shown in the present study that hydroxycobalamin (a form of vitamin B12, HOCbl), which incorporates cobalt, significantly enhances the cytotoxicity of diethyldithiocarbamate (DDC), decreasing its IC50 value in tumor cells three to five times. The addition of HOCbl to aqueous DDC solutions accelerated the reduction of oxygen. No hydrogen peroxide accumulation was observed in DDC + HOCbl solutions; however, catalase slowed down the oxygen reduction rate. Catalase as well as the antioxidants N-acetylcysteine (NAC) and glutathione (GSH) partially inhibited the cytotoxic effect of DDC + HOCbl, whereas ascorbate, pyruvate, and tiron, a scavenger of superoxide anion, had no cytoprotective effect. The administration of HOCbl into DDC solutions (> 1 mM) resulted in the formation of a crystalline precipitate, which was inhibited in the presence of GSH. The data of UV and NMR spectroscopy and HPLC and Mass Spectrometry (LC/MS) indicated that the main products of the reaction of DDC with HOCbl are disulfiram (DSF) and its oxidized forms, sulfones and sulfoxides. The increase in the cytotoxicity of DDC combined with HOCbl occurred both in the presence of Cu2+ in culture medium and in nominally Cu-free solutions, as well as in growth medium containing the copper chelator bathocuproine disulfonate (BCS). The results indicate that HOCbl accelerates the oxidation of DDC with the formation of DSF and its oxidized forms. Presumably, the main cause of the synergistic increase in the toxic effect of DDC + HOCbl is the formation of sulfones and sulfoxides of DSF.
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Metals in Medicine: The Therapeutic Use of Metal Ions in the Clinic.
Carver, PL
Metal ions in life sciences. 2019
Abstract
Metal ions are indispensable for living organisms. However, the roles of metal ions in humans is complex, and remains poorly understood. Imbalances in metal ion levels, due to genetic or environmental sources, are associated with a number of significant health issues. However, in clinical medicine, the role of metal ions and metal-based drugs is notable in three major areas: as metal-related diseases; as metal-based medicines (including drugs, imaging agents, and metal chelators); and as agents of metal-based toxicity.