Inflammation,It’s Regulation and Antiphlogistic Effect of the Cyanogenic Glycoside Amygdalin

The inflammatory reaction accompanies in part or in full any disease process in the vascularized metazoan. This complicated reaction is controlled by regulatory mechanisms, some of which produce unpleasant symptomatic manifestations of inflammation. Therefore, there has been an effort to develop selective drugs aimed at removing pain, fever, or swelling. Gradually, however, serious adverse side effects of such inhibitors became apparent. Scientific research has therefore continued to explore new possibilities, including naturally available substances. Amygdalin is a cyanogenic glycoside present, e.g., in bitter almonds. This glycoside has already sparked many discussions among scientists, especially about its anticancer potential and related toxic cyanides. However, toxicity at different doses made it generally unacceptable. Although amygdalin given at the correct oral dose may not lead to poisoning, it has not yet been accurately quantified, as its action is often affected by different intestinal microbial consortia. Its pharmacological activities have been studied, but its effects on the body’s inflammatory response are lacking. This review discusses the chemical structure, toxicity, and current knowledge of the molecular mechanism of amygdalin activity on immune functions, including the anti-inflammatory effect, but also discusses inflammation as such, its mediators with diverse functions, which are usually targeted by drugs.     

The Role of Triazole and Glucose Moieties in Alkali Metal Cation Complexation by Lower-Rim Tertiary-Amide Calix[4]arene Derivatives

The binding of alkali metal cations with two tertiary-amide lower-rim calix[4]arenes was studied in methanol, N,N-dimethylformamide, and acetonitrile in order to explore the role of triazole and glucose functionalities in the coordination reactions. The standard thermodynamic complexation parameters were determined microcalorimetrically and spectrophotometrically. On the basis of receptor dissolution enthalpies and the literature data, the enthalpies for transfer of reactants and products between the solvents were calculated. The solvent inclusion within a calixarene hydrophobic basket was explored by means of ¹H NMR spectroscopy. Classical molecular dynamics of the calixarene ligands and their complexes were carried out as well. The affinity of receptors for cations in methanol and N,N-dimethylformamide was quite similar, irrespective of whether they contained glucose subunits or not. This indicated that sugar moieties did not participate or influence the cation binding. All studied reactions were enthalpically controlled. The peak affinity of receptors for sodium cation was noticed in all complexation media. The complex stabilities were the highest in acetonitrile, followed by methanol and N,N-dimethylformamide. The solubilities of receptors were greatly affected by the presence of sugar subunits. The medium effect on the affinities of calixarene derivatives towards cations was thoroughly discussed regarding the structural properties and solvation abilities of the investigated solvents.     

Magnetic Force Formulae for Magnets at Small Distances

In [7], the magnetic force on subregions of rigid magnetized bodies was studied as a discrete-to-continuum limit. The derived force formula includes a new term, which depends on the underlying crystalline lattice structure ℒ. It originates from contributions of magnetic dipole-dipole interactions of dipole moments close to the boundary of the considered subregion. Further studies of this new term have led to the question of how the magnetic force between two idealized magnets, which are a distance ε > 0 apart, depends on ε as ε → 0. In this article, analytical aspects of this question are discussed, cf. [5], where also numerical experiments are performed. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

An Osteosarcoma Stem Cell Potent Nickel(II)-Polypyridyl Complex Containing Flufenamic Acid

Apoptosis resistance is inherent to stem cell-like populations within tumours and is one of the major reasons for chemotherapy failures in the clinic. Necroptosis is a non-apoptotic mode of programmed cell death that could help bypass apoptosis resistance. Here we report the synthesis, characterisation, biophysical properties, and anti-osteosarcoma stem cell (OSC) properties of a new nickel(II) complex bearing 3,4,7,8-tetramethyl-1,10-phenanthroline and two flufenamic acid moieties, 1. The nickel(II) complex 1 is stable in both DMSO and cell media. The nickel(II) complex 1 kills bulk osteosarcoma cells and OSCs grown in monolayer cultures and osteospheres grown in three-dimensional cultures within the micromolar range. Remarkably, 1 exhibits higher potency towards osteospheres than the metal-based drugs used in current osteosarcoma treatment regimens, cisplatin and carboplatin, and an established anti-cancer stem cell agent, salinomycin (up to 7.7-fold). Cytotoxicity studies in the presence of prostaglandin E2 suggest that 1 kills OSCs in a cyclooxygenase-2 (COX-2) dependent manner. Furthermore, the potency of 1 towards OSCs decreased significantly upon co-treatment with necrostatin-1 or dabrafenib, well-known necroptosis inhibitors, implying that 1 induces necroptosis in OSCs. To the best of our knowledge, 1 is the first compound to implicate both COX-2 and necroptosis in its mechanism of action in OSCs.     

Dynamical time versus system's time in quantum mechanics

Properties of an operator representing the dynamical time in the extended parameterization invariant formulation of quantum mechanics are studied. It is shown that this time operator is given by a positive operator measure analogously to the quantities that are known to represent various measurable time operators. The relation between the dynamical time of the extended formulation and the best known example of the system's time operator, i.e., for the free one-dimensional particle, is obtained.     

Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment

A series of tripeptides TrpTrpPhe (1), TrpTrpTyr (2), and TrpTrpTyr[CH₂N(CH₃)₂] (3) were synthesized, and their photophysical properties and non-covalent binding to polynucleotides were investigated. Fluorescent Trp residues (quantum yield in aqueous solvent Φ_F = 0.03–0.06), allowed for the fluorometric study of non-covalent binding to DNA and RNA. Moreover, high and similar affinities of 2×HCl and 3×HCl to all studied double stranded (ds)-polynucleotides were found (logK_a = 6.0–6.8). However, the fluorescence spectral responses were strongly dependent on base pair composition: the GC-containing polynucleotides efficiently quenched Trp emission, at variance to AT- or AU-polynucleotides, which induced bisignate response. Namely, addition of AT(U) polynucleotides at excess over studied peptide induced the quenching (attributed to aggregation in the grooves of polynucleotides), whereas at excess of DNA/RNA over peptide the fluorescence increase of Trp was observed. The thermal denaturation and circular dichroism (CD) experiments supported peptides binding within the grooves of polynucleotides. The photogenerated quinone methide (QM) reacts with nucleophiles giving adducts, as demonstrated by the photomethanolysis (quantum yield Φ_R = 0.11–0.13). Furthermore, we have demonstrated photoalkylation of AT oligonucleotides by QM, at variance to previous reports describing the highest reactivity of QMs with the GC reach regions of polynucleotides. Our investigations show a proof of principle that QM precursor can be imbedded into a peptide and used as a photochemical switch to enable alkylation of polynucleotides, enabling further applications in chemistry and biology.     

Radioactivity in Montenegro beach sands and assessment of the corresponding environmental risk

Activity concentrations of the naturally occurring radionuclides ²²⁶Ra, ²³²Th, ⁴⁰K and anthropogenic ¹³⁷Cs in sand samples collected from 20 renowned beaches on the Coast of Montenegro have been determined using an HPGe (high purity Ge spectrometer). The average activity concentrations were found to be 7.4, 5.2, 97.3 and 0.5 Bq kg^?1, respectively. For all sand samples, the radium equivalent activity has been evaluated and found to be lower than the limit of 370 Bq kg^?1. External and internal hazard indices were less than unity. The gonadal dose equivalent was estimated to be on average 75 μSv y^?1, which is about four times lower than the global average for soil (0.3 mSv y^?1). Calculated values of absorbed dose rates showed the range from 3.1 to 28 nGy h^?1, which is below the world median of average values (57 nGy h^?1). The effective dose rate in the range from 3.8 to 34.4 μSv y^?1 was significantly below the recommended limit value for the public (1 mSv y^?1). The highest dose rate was found for the Velika Plaza locality, which also showed heavy metal contents (As, B, Cd, Hg, Cr, Cu, Mn, Ni, Pb, Zn and Ba) significantly higher than in the sand from Jaz, a locality with one of the lowest dose rates.     

A Molecular Approach for Unraveling Surface Phase Transitions: Sulfation of BaO as a Model NO(x) Trap

SO(3) -induced surface reconstruction: The SO(3) molecule as a multidentate ligand induces remarkable surface reconstruction phenomena on alkaline earth oxide surface. By using ab initio computations, adsorption properties are derived to elucidate the thermodynamics of the SO(3) -BaO system.