FMR and voltage induced transport in normal metal-ferromagnet-superconductor trilayers

We study the subgap spin and charge transport in normal metal-ferromagnet-superconductor trilayers induced by bias voltage and/or magnetization precession. Transport properties are discussed in terms of time-dependent scattering theory. We assume the superconducting gap is small on the energy scales set by the Fermi energy and the ferromagnetic exchange splitting, and compute the non-equilibrium charge and spin current response to first order in precession frequency, in the presence of a finite applied voltage. We find that the voltage-induced instantaneous charge current and longitudinal spin current are unaffected by the precessing magnetization, while the pumped transverse spin current is determined by spin-dependent conductances and details of the electron-hole scattering matrix. A simplified expression for the transverse spin current is derived for structures where the ferromagnet is longer than the transverse spin coherence length.Comment: 10 page

Endogenous Isoquinoline Alkaloids Agonists of Acid-Sensing Ion Channel Type 3

Acid-sensing ion channels (ASICs) ASIC3 expressed mainly in peripheral sensory neurons play an important role in pain perception and inflammation development. In response to acidic stimuli, they can generate a unique biphasic current. At physiological pH 7.4, human ASIC3 isoform (hASIC3) is desensitized and able to generate only a sustained current. We found endogenous isoquinoline alkaloids (EIAs), which restore hASIC3 from desensitization and recover the transient component of the current. Similarly, rat ASIC3 isoform (rASIC3) can also be restored from desensitization (at pH < 7.0) by EIAs with the same potency. At physiological pH and above, EIAs at high concentrations were able to effectively activate hASIC3 and rASIC3. Thus, we found first endogenous agonists of ASIC3 channels that could both activate and prevent or reverse desensitization of the channel. The decrease of EIA levels could be suggested as a novel therapeutic strategy for treatment of pain and inflammation

Endogenous Neuropeptide Nocistatin Is a Direct Agonist of Acid-Sensing Ion Channels (ASIC1, ASIC2 and ASIC3)

Acid-sensing ion channel (ASIC) channels belong to the family of ligand-gated ion channels known as acid-sensing (proton-gated) ion channels. Only a few activators of ASICs are known. These are exogenous and endogenous molecules that cause a persistent, slowly desensitized current, different from an acid-induced current. Here we describe a novel endogenous agonist of ASICs—peptide nocistatin produced by neuronal cells and neutrophils as a part of prepronociceptin precursor protein. The rat nocistatin evoked currents in X. laevis oocytes expressing rat ASIC1a, ASIC1b, ASIC2a, and ASIC3 that were very similar in kinetic parameters to the proton-gated response. Detailed characterization of nocistatin action on rASIC1a revealed a proton-like dose-dependence of activation, which was accompanied by a dose-dependent decrease in the sensitivity of the channel to the protons. The toxin mambalgin-2, antagonist of ASIC1a, inhibited nocistatin-induced current, therefore the close similarity of mechanisms for ASIC1a activation by peptide and protons could be suggested. Thus, nocistatin is the first endogenous direct agonist of ASICs. This data could give a key to understanding ASICs activation regulation in the nervous system and also could be used to develop new drugs to treat pathological processes associated with ASICs activation, such as neurodegeneration, inflammation, and pain

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

Plant lignans exhibit a wide range of biological activities, which makes them the research objects of potential use as therapeutic agents. They provide diverse naturally-occurring pharmacophores and are available for production by chemical synthesis. A large amount of accumulated data indicates that lignans of different structural groups are apt to demonstrate both anti-inflammatory and antioxidant effects, in many cases, simultaneously. In this review, we summarize the comprehensive knowledge about lignan use as a bioactive agent in disorders associated with oxidative stress and inflammation, pharmacological effects in vitro and in vivo, molecular mechanisms underlying these effects, and chemical synthesis approaches. This article provides an up-to-date overview of the current data in this area, available in PubMed, Scopus, and Web of Science databases, screened from 2000 to 2022

Analysis of Structural Determinants of Peptide MS 9a-1 Essential for Potentiating of TRPA1 Channel

The TRPA1 channel is involved in a variety of physiological processes and its activation leads to pain perception and the development of inflammation. Peptide Ms 9a-1 from sea anemone Metridium senile is a positive modulator of TRPA1 and causes significant analgesic and anti-inflammatory effects by desensitization of TRPA1-expressing sensory neurons. For structural and functional analysis of Ms 9a-1, we produced four peptides—Ms 9a-1 without C-terminal domain (abbreviated as N-Ms), short C-terminal domain Ms 9a-1 alone (C-Ms), and two homologous peptides (Ms 9a-2 and Ms 9a-3). All tested peptides possessed a reduced potentiating effect on TRPA1 compared to Ms 9a-1 in vitro. None of the peptides reproduced analgesic and anti-inflammatory properties of Ms 9a-1 in vivo. Peptides N-Ms and C-Ms were able to reduce pain induced by AITC (selective TRPA1 agonist) but did not decrease AITC-induced paw edema development. Fragments of Ms 9a-1 did not effectively reverse CFA-induced thermal hyperalgesia and paw edema. Ms 9a-2 and Ms 9a-3 possessed significant effects and anti-inflammatory properties in some doses, but their unexpected efficacy and bell-shape dose–responses support the hypothesis of other targets involved in their effects in vivo. Therefore, activity comparison of Ms 9a-1 fragments and homologues peptides revealed structural determinants important for TRPA1 modulation, as well as analgesic and anti-inflammatory properties of Ms9a-1

Anti-Inflammatory and Analgesic Effects of TRPV1 Polypeptide Modulator APHC3 in Models of Osteo- and Rheumatoid Arthritis

Arthritis is a widespread inflammatory disease associated with progressive articular surface degradation, ongoing pain, and hyperalgesia causing the development of functional limitations and disability. TRPV1 channel is one of the high-potential targets for the treatment of inflammatory diseases. Polypeptide APHC3 from sea anemone Heteractis crispa is a mode-selective TRPV1 antagonist that causes mild hypothermia and shows significant anti-inflammatory and analgesic activity in different models of pain. We evaluated the anti-inflammatory properties of APHC3 in models of monosodium iodoacetate (MIA)-induced osteoarthritis and complete Freund’s adjuvant (CFA)-induced rheumatoid monoarthritis in comparison with commonly used non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, and meloxicam. Subcutaneous administration of APHC3 (0.1 mg/kg) significantly reversed joint swelling, disability, grip strength impairment, and thermal and mechanical hypersensitivity. The effect of APHC3 was equal to or better than that of reference NSAIDs. Protracted treatment with APHC3 decreased IL-1b concentration in synovial fluid, reduced inflammatory changes in joints, and prevented the progression of cartilage degradation. Therefore, polypeptide APHC3 has the potential to be an analgesic and anti-inflammatory substance for the alleviation of arthritis symptoms

Retinoic Acid-Differentiated Neuroblastoma SH-SY5Y Is an Accessible In Vitro Model to Study Native Human Acid-Sensing Ion Channels 1a (ASIC1a)

Human neuroblastoma SH-SY5Y is a prominent neurobiological tool used for studying neuropathophysiological processes. We investigated acid-sensing (ASIC) and transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1) ion channels present in untreated and differentiated neuroblastoma SH-SY5Y to propose a new means for their study in neuronal-like cells. Using a quantitative real-time PCR and a whole-cell patch-clamp technique, ion channel expression profiles, functionality, and the pharmacological actions of their ligands were characterized. A low-level expression of ASIC1a and ASIC2 was detected in untreated cells. The treatment with 10 μM of retinoic acid (RA) for 6 days resulted in neuronal differentiation that was accompanied by a remarkable increase in ASIC1a expression, while ASIC2 expression remained almost unaltered. In response to acid stimuli, differentiated cells showed prominent ASIC-like currents. Detailed kinetic and pharmacological characterization suggests that homomeric ASIC1a is a dominant isoform among the present ASIC channels. RA-treatment also reduced the expression of TRPV1 and TRPA1, and minor electrophysiological responses to their agonists were found in untreated cells. Neuroblastoma SH-SY5Y treated with RA can serve as a model system to study the effects of different ligands on native human ASIC1a in neuronal-like cells. This approach can improve the characterization of modulators for the development of new neuroprotective and analgesic drugs

Hydrophilization and Functionalization of Fullerene C₆₀ with Maleic Acid Copolymers by Forming a Non-Covalent Complex

In this study, we report an easy approach for the production of aqueous dispersions of C60 fullerene with good stability. Maleic acid copolymers, poly(styrene-alt-maleic acid) (SM), poly(N-vinyl-2-pyrrolidone-alt-maleic acid) (VM) and poly(ethylene-alt-maleic acid) (EM) were used to stabilize C60 fullerene molecules in an aqueous environment by forming non-covalent complexes. Polymer conjugates were prepared by mixing a solution of fullerene in N-methylpyrrolidone (NMP) with an aqueous solution of the copolymer, followed by exhaustive dialysis against water. The molar ratios of maleic acid residues in the copolymer and C60 were 5/1 for SM and VM and 10/1 for EM. The volume ratio of NMP and water used was 1:1.2–1.6. Water-soluble complexes (composites) dried lyophilically retained solubility in NMP and water but were practically insoluble in non-polar solvents. The optical and physical properties of the preparations were characterized by UV-Vis spectroscopy, FTIR, DLS, TGA and XPS. The average diameter of the composites in water was 120–200 nm, and the ξ-potential ranged from −16 to −20 mV. The bactericidal properties of the obtained nanostructures were studied. Toxic reagents and time-consuming procedures were not used in the preparation of water-soluble C60 nanocomposites stabilized by the proposed copolymers