Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution.

Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells-Dawson polyoxometalate, α-KPWO20HO (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol).

In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography.

In this study, we demonstrate for the first time, that a discrete metal-oxo cluster α-/β-KPWO (WD-POM) exhibits superior performance as a computed tomography (CT) contrast agent, in comparison to the standard contrast agent iohexol. A toxicity evaluation of WD-POM was performed according to standard toxicological protocols using Wistar albino rats. The maximum tolerable dose (MTD) of 2000 mg/kg was initially determined after oral WD-POM application.

Comparative Evaluation of [F]5-Fluoroaminosuberic Acid and (4)-4-3-[F]fluoropropyl)-l-Glutamate as System xC--Targeting Radiopharmaceuticals.

System [Formula: see text] is an appealing biomarker for targeting oxidative stress with oncologic PET imaging and can serve as an alternative PET biomarker to other metabolic indicators. In this paper, we report a direct comparison of 2 F-labeled amino acid radiopharmaceuticals targeting system [Formula: see text], [F]5-fluoroaminosuberic acid ([F]FASu) and (4)-4-(3-[F]fluoropropyl)-l-glutamate ([F]FSPG), in terms of their uptake specificity and ability to image glioma and lung cancer xenografts in vivo. Both tracers were synthesized according to previously published procedures.

The simultaneous action of acute paradoxical sleep deprivation and hypothyroidism modulates synaptosomal ATPases and acetylcholinesterase activities in rat brain.

Background: Thyroid dysfunctions as well as sleep abnormalities are usually followed by neurological, psychiatric and/or behavioral disorders. On the other hand, changes in the brain adenosine triphosphatases (ATPases) and acetylcholinesterase (AChE) activities show significant importance in pathogenetic pathways in the evolution of numerous neuropsychiatric diseases.

Methods: This study aimed to evaluate the in vivo simultaneous effects of hypothyroidism and paradoxical sleep deprivation for 72 h on synaptosomalATPases and AChE activities of whole rat brains.

Selected polyoxopalladates as promising and selective antitumor drug candidates.

Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na[PdAsO(OH)]·42HO (Pd), Na[SrPdO(OH)(PhAsO)(OAc)]·2NaOAc·32HO (SrPd), Na[Pd(AsPh)O]·23HO (PdL), Na[SnOPd(PO)]·43HO (SnPd), and Na[PbOPd(PO)]·38HO (PbPd)), as the largest subset of PONMs. A pure inorganic, Pd, was found as the most potent and selective antineuroblastoma agent with IC values (µM) of 7.

New Insights into Antibacterial and Antifungal Properties, Cytotoxicity and Aquatic Ecotoxicity of Flame Retardant PA6/DOPO-Derivative Nanocomposite Textile Fibers.

The aim of this study was to evaluate the antibacterial and antifungal activity, cytotoxicity, leaching, and ecotoxicity of novel flame retardant polyamide 6 (PA6) textile fibers developed by our research group. The textile fibers were produced by the incorporation of flame-retardant bridged 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) derivative (PHED) in the PA6 matrix during the in situ polymerization process at concentrations equal to 10 and 15 wt% (PA6/10PHED and PA6/15PHED, respectively). Whilst the nanodispersed PHED provided highly efficient flame retardancy, its biological activity led to excellent antibacterial activity against and , as well as excellent antifungal activity against and .

Characterization of Polyamide 6/Multilayer Graphene Nanoplatelet Composite Textile Filaments Obtained Via In Situ Polymerization and Melt Spinning.

Studies of the production of fiber-forming polyamide 6 (PA6)/graphene composite material and melt-spun textile fibers are scarce, but research to date reveals that achieving the high dispersion state of graphene is the main challenge to nanocomposite production. Considering the significant progress made in the industrial mass production of graphene nanoplatelets (GnPs), this study explored the feasibility of production of PA6/GnPs composite fibers using the commercially available few-layer GnPs. To this aim, the GnPs were pre-dispersed in molten -caprolactam at concentrations equal to 1 and 2 wt %, and incorporated into the PA6 matrix by the in situ water-catalyzed ring-opening polymerization of -caprolactam, which was followed by melt spinning.

A new acetylcholinesterase allosteric site responsible for binding voluminous negatively charged molecules - the role in the mechanism of AChE inhibition.

Acetylcholinesterase (AChE) inhibitors are important in the treatment of neurodegenerative diseases. Two inhibitors, 12-tungstosilicic acid (WSiA) and 12-tungstophosphoric acid (WPA), which have polyoxometalate (POM) type structure, have been shown to inhibit AChE activity in nM concentration. Circular dichroism and tryptophan fluorescence spectroscopy demonstrated that the AChE inhibition was not accompanied by significant changes in the secondary structure of the enzyme.

Analytical techniques for multiplex analysis of protein biomarkers.

Introduction: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways.

Effect of Different Flame-Retardant Bridged DOPO Derivatives on Properties of in Situ Produced Fiber-Forming Polyamide 6.

The production of sustainable and effective flame retardant (FR) polyamide 6 (PA6) fibrous materials requires the establishment of a novel approach for the production of polyamide 6/FR nanodispersed systems. This research work explores the influence of three different flame-retardant bridged 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) derivatives on the comprehensive properties of in situ produced PA6/FR systems. To this end, in situ water-catalyzed ring-opening polymerization of -caprolactam was conducted in the presence of three different bridged DOPO derivatives, e.

Tailored Crosslinking Process and Protective Efficiency of Epoxy Coatings Containing Glycidyl-POSS.

Versatile product protective coatings that deliver faster drying times and shorter minimum overcoat intervals that enable curing at faster line speeds and though lower energy consumption are often desired by coating manufacturers. Product protective coatings, based on silsesquioxane-modified diglycidyl ether of bisphenol-A (DGEBA) epoxy resin, are prepared through a glycidyl ring-opening polymerization using dicyandiamide (DICY) as a curing agent. As silsesquioxane modifier serves the octaglycidyl-polyhedral oligomeric silsesquioxane (GlyPOSS).

toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using rats as a model system.

In this study, the hypoglycemic effect of a donut-shaped polyanion salt (NH)[Na@PWO]·31HO {NaPW} and its Ag-containing derivative K[Ag@PWO]·22HO·6KCl {AgPW}, as well as their hepatotoxicity and nephrotoxicity, was evaluated. In the screening hypoglycemic study, rats with streptozotocin induced diabetes were treated intraperitoneally with three single doses (5, 10, and 20 mg per kg per b.w.

The Effect of Chirality on the Application of 5-[F]Fluoro-Aminosuberic Acid ([F]FASu) for Oxidative Stress Imaging.

Purpose: The cystine transporter, system x, plays a crucial role in sustaining redox homeostasis and is reported to be overexpressed in several cancer subtypes. 5-[F]Fluoroaminosuberic acid ([F]FASu) is a novel positron emission tomography (PET) tracer, which exhibits specific uptake via system x. [F]FASu synthesis by the commonly used Kryptofix 2.

Polyoxometalates in Biomedicine: Update and Overview.

Background: Polyoxometalates (POMs) are negatively charged metal-oxo clusters of early transition metal ions in high oxidation states (e.g., WVI, MoVI, VV).

Tetravalent Metal Ion Guests in Polyoxopalladate Chemistry: Synthesis and Anticancer Activity of [MOPd(PO)] (M = Sn, Pb).

The first two examples of polyoxopalladates(II) (POPs) containing tetravalent metal ion guests, [MOPd(PO)] (M = Sn, Pb), have been prepared and structurally characterized in the solid state, solution, and gas phase. The interactions of the metal ion guests and the palladium-oxo shell were studied by theoretical calculations. The POPs were shown to possess anticancer activity by causing oxidative stress inducing caspase activation and consecutive apoptosis of leukemic cells.

Experimental and theoretical insights of functionalized hexavanadates on Na/K-ATPase activity; molecular interaction field, ab initio calculations and in vitro assays.

The influence of three functionalized hexavanadates (V): Na [VO{(OCH)CCH}], [H] [VO{(OCH)CCHOCOCHCH}] and [(CH)N] [VO{(OCH)CCHOOC(CH)-COOH} on Na/K-ATPase activity, was investigated in vitro. Including compounds already tested by Xu et al. (Journal of Inorganic Biochemistry 161 (2016) 27-36), all functionalized hexavanadates inhibit the activity of Na/K-ATPase in a dose-dependent manner but with different inhibitory potencies.

Cystine/glutamate antiporter xCT (SLC7A11) facilitates oncogenic RAS transformation by preserving intracellular redox balance.

The family of proto-oncogenes are among the most commonly mutated genes in human cancers and predict poor clinical outcome. Several mechanisms underlying oncogenic RAS transformation are well documented, including constitutive signaling through the RAF-MEK-ERK proproliferative pathway as well as the PI3K-AKT prosurvival pathway. Notably, control of redox balance has also been proposed to contribute to RAS transformation.

Non-invasive Use of Positron Emission Tomography to Monitor Diethyl maleate and Radiation-Induced Changes in System x Activity in Breast Cancer.

Purpose: The system x transporter is upregulated in cancer cells in response to oxidative stress (OS). 5-[F]fluoroaminosuberic acid ([F]FASu) has been reported as a novel positron emission tomography (PET) imaging agent, targeting system x. The goal of this study was to evaluate the utility of [F]FASu in monitoring cellular response to diethyl maleate (DEM) and radiation-induced OS fluctuations.

F-Branched-Chain Amino Acids: Structure-Activity Relationships and PET Imaging Potential.

The large, neutral L-type amino acid transporters (LAT1-LAT4) are sodium-independent transporters that are widely distributed throughout the body. LAT expression levels are increased in many types of cancer, and their expression increases as cancers progress, leading to high expression levels in high-grade tumors and metastases. Because of the key role and overexpression of LAT in many types of cancer, radiolabeled LAT substrates are promising candidates for nuclear imaging of malignancies that are not well revealed by conventional radiotracers.

Synthesis and evaluation of an F-labeled boramino acid analog of aminosuberic acid for PET imaging of the antiporter system x.

In this study, we synthesized F-ASu-BF, a close boramino acid analog of 5-[F]fluoro-aminosuberic acid (F-ASu), via F-F isotope exchange reaction and evaluated its potential for imaging with positron emission tomography (PET). F-ASu-BF was stable in mouse plasma and taken up into PC3 prostate cancer cells via the system x amino acid transporter. The continuous use of isoflurane for anesthesia during dynamic imaging acquisition slowed down the excretion of F-ASu-BF and enabled visualization of PC3 tumor xenografts in mice.

Modulation of rat synaptosomal ATPases and acetylcholinesterase activities induced by chronic exposure to the static magnetic field.

Purpose: It is considered that exposure to static magnetic fields (SMF) may have both detrimental and therapeutic effect, but the mechanism of SMF influence on the living organisms is not well understood. Since the adenosine triphosphatases (ATPases) and acetylcholinesterase (AChE) are involved in both physiological and pathological processes, the modulation of Na/K-ATPase, ecto-ATPases and AChE activities, as well as oxidative stress responses were followed in synaptosomes isolated from rats after chronic exposure toward differently oriented SMF.

Material And Methods: Wistar albino rats were randomly divided into three experimental groups (six animals per group): Up and Down group - exposed to upward and downward oriented SMF, respectively, and Control group.

Pharmacological characterisation of CR6086, a potent prostaglandin E receptor 4 antagonist, as a new potential disease-modifying anti-rheumatic drug.

Background: Prostaglandin E (PGE) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes.

Synthesis and evaluation of bifunctional tetrahydroxamate chelators for labeling antibodies with Zr for imaging with positron emission tomography.

Two novel bifunctional tetrahydroxamate chelators 3 and 4 were synthesized and evaluated for labeling antibodies with Zr for positron emission tomography imaging. Compared to previously reported tetrahydroxamate chelators 1 and 2 with an iminodiacetamide backbone, 3 and 4 were based on an extended iminodipropionamide and dipropylenetriamine backbone, respectively. Trastuzumab conjugates of 3 and 4 were efficiently labeled with Zr (>95% radiochemical yield).

Subchronic methionine load induces oxidative stress and provokes biochemical and histological changes in the rat liver tissue.

The aim of this study was to assess the effects of L-cysteine (Cys) (7 mg/kg) and N-acetyl-L-cysteine (NAC) (50 mg/kg) in the rat liver caused by subchronic i.p. application of methionine (Met) (0.