Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase).     

Polythiophene nanoparticles in aqueous media

The article presents the data concerning the synthesis of polythiophene (PTh) nanoparticles in aqueous medium applying emulsion polymerization. The synthetic method was studied in variety of combinations of initiator and surfactant. It was found that application of potassium peroxydisulfate (KPS) as initiator and sodium dodecyl sulfate (SDS) as the surfactant gives the best product yields. The structure, morphology, and physicochemical properties have been analyzed showing that the resulting latex have conducting film forming properties. Resulting polymers were characterized via fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), thermogravimetry‐differential thermal analysis (TG‐DTA), differential scanning calorimetry (DSC), and electrochemical methods [e.g. current–voltage characteristics (I–V), activation energy of electric conductivity, and doping processes]. A mechanism of the polymerization reaction is also discussed. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43495.     

Novel Furin Inhibitors with Potent Anti‐infectious Activity

New peptidomimetic furin inhibitors with unnatural amino acid residues in the P3 position were synthesized. The most potent compound 4‐guanidinomethyl‐phenylacteyl‐Arg‐Tle‐Arg‐4‐amidinobenzylamide (MI‐1148) inhibits furin with a K_i value of 5.5 pM . The derivatives also strongly inhibit PC1/3, whereas PC2 is less affected. Selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. A significant protective effect against anthrax and diphtheria toxin was observed in the presence of the furin inhibitors. Furthermore, the spread of the highly pathogenic H5N1 and H7N1 avian influenza viruses and propagation of canine distemper virus was strongly inhibited. Inhibitor MI‐1148 was crystallized in complex with human furin. Its N‐terminal guanidinomethyl group in the para position of the P5 phenyl ring occupies the same position as that found previously for a structurally related inhibitor containing this substitution in the meta position, thereby maintaining all of the important P5 interactions. Our results confirm that the inhibition of furin is a promising strategy for a short‐term treatment of acute infectious diseases.     

Covalent dyads of porphyrin-fullerene and perylene-fullerene for organic photovoltaics: Spectroscopic and photocurrent studies

Supermolecular complexes of zinc porphyrin or perylenediimide as covalent dyads with fullerene (C₆₀) in chloroform and as Langmuir-Blodgett layers on an Au substrate were studied. In our studies we have used following spectroscopic methods: electronic absorption, fluorescence and electron spin resonance in solution. Also infrared absorption spectra in a KBr pellet and reflectance-absorption in Langmuir-Blodgett layers were monitored. Photocurrent generation in a photoelectrochemical cell was also studied. The redistribution of charge both upon porphyrin linkage to C₆₀ and when the systems are deposited on the Au substrate was shown. Photocurrent examinations show a great influence of the fullerene presence on photoresponse of the systems.     

Untersuchungen zur Löslichkeit,Korngrenzensegregation und chemisch-analytischen Bestimmung des Tellurs im Eisen

Die Löslichkeit von Tellur in Eisen wurde durch licht- und elektronenmikroskopische Prüfung von Fe–Te-Legierungen auf Ausscheidungen bestimmt. In α-Eisen bei 700°C sind etwa 50 ppm und bei 850°C 120 ppm löslich, in γ-Eisen lösen sich bei 930°C 5 ppm und bei 1000°C 22 ppm Te. Bei höheren Konzentrationen wird FeTe_0,9 festgestellt. In Fe–Mn–Te-Legierungen wird das Te als Mangantellurid gebunden, dieses bildet Einschlüsse gemeinsam mit Mangansulfid. In Fe–Ti–Te-Legierungen wird nur ein kleiner Anteil Te in Titansulfiden gelöst. Tellur segregiert an die Korngrenzen von α- und γ-Eisen und bewirkt interkristallinen Bruch. Die mit AES bestimmten Korngrenzenkonzentrationen nehmen mit der Lösungskonzentration zu und erreichen bei Überschreiten der Löslichkeit einen Sättigungswert. Die Korngrenzensegregation nimmt mit zunehmender Temperatur ab. Tellur bewirkt eine auffallende Facettierung der Korngrenzflächen, es entstehen Strukturen mit Terrassen und Stufen. Die Proben brechen hierdurch bereits während der Auslagerung an den Korngrenzen auf und zeigen Kornzerfall. In Mn-haltigen Proben wird keine Korngrenzensegregation des Te beobachtet, wenn das Tellur völlig vom Mangan abgebunden ist; in diesem Fall ist der interkristalline Anteil der Bruchflächen sehr gering. Die chemische Bestimmung von Tellur in Eisen und Stählen kann sehr vorteilhaft mit der Atomabsorptionsspektroskopie durchgeführt werden, es wurden die Flammen- und die Graphitrohrmethode untersucht. Die Bestimmung kleiner Tellurgehalte in Stählen durch Atomisieren im Graphitrohr wird durch Chlorid, Chrom, Mangan und Nickel beeinflußt. Zu einer deutlichen Optimierung des Atomisierungsablaufs führt das Atomisieren von einer in das Graphitrohr eingeführten Plattform. Lediglich Mangan vermindert dann die Intensität des Absorptionssignals. Es wird eine Nachweisgrenze von 0,2 ppm Tellur bei einer relativen Standardabweichung von 30% erreicht. Mit der Flammentechnik gelingt die Bestimmung bis zu 50 ppm Tellur.     

Design,Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin

The activation of viral glycoproteins by the host protease furin is an essential step in the replication of numerous pathogenic viruses. Thus, effective inhibitors of furin could serve as broad-spectrum antiviral drugs. A crystal structure of an inhibitory hexapeptide derivative in complex with furin served as template for the rational design of various types of new cyclic inhibitors. Most of the prepared derivatives are relatively potent furin inhibitors with inhibition constants in the low nanomolar or even sub-nanomolar range. For seven derivatives the crystal structures in complex with furin could be determined. In three complexes, electron density was found for the entire inhibitor. In the other cases the structures could be determined only for the P6/P5-P1 segments, which directly interact with furin. The cyclic derivatives together with two non-cyclic reference compounds were tested as inhibitors of the proteolytic activation and replication of respiratory syncytial virus in cells. Significant antiviral activity was found for both linear reference inhibitors, whereas a negligible efficacy was determined for the cyclic derivatives.     

De Novo Missense Mutations in TNNC1 and TNNI3 Causing Severe Infantile Cardiomyopathy Affect Myofilament Structure and Function and Are Modulated by Troponin Targeting Agents

Rare pediatric non-compaction and restrictive cardiomyopathy are usually associated with a rapid and severe disease progression. While the non-compaction phenotype is characterized by structural defects and is correlated with systolic dysfunction, the restrictive phenotype exhibits diastolic dysfunction. The molecular mechanisms are poorly understood. Target genes encode among others, the cardiac troponin subunits forming the main regulatory protein complex of the thin filament for muscle contraction. Here, we compare the molecular effects of two infantile de novo point mutations in TNNC1 (p.cTnC-G34S) and TNNI3 (p.cTnI-D127Y) leading to severe non-compaction and restrictive phenotypes, respectively. We used skinned cardiomyocytes, skinned fibers, and reconstituted thin filaments to measure the impact of the mutations on contractile function. We investigated the interaction of these troponin variants with actin and their inter-subunit interactions, as well as the structural integrity of reconstituted thin filaments. Both mutations exhibited similar functional and structural impairments, though the patients developed different phenotypes. Furthermore, the protein quality control system was affected, as shown for TnC-G34S using patient’s myocardial tissue samples. The two troponin targeting agents levosimendan and green tea extract (-)-epigallocatechin-3-gallate (EGCg) stabilized the structural integrity of reconstituted thin filaments and ameliorated contractile function in vitro in some, but not all, aspects to a similar degree for both mutations.     

Synthesis and functional characterization of tridegin and its analogues: inhibitors and substrates of factor XIIIa

Tridegin, a 66‐mer peptide isolated from the leech Haementeria ghilianii, is a potent inhibitor of the coagulation factor XIIIa. This paper describes the chemical synthesis of tridegin by two different strategies—solid‐phase assembly and native chemical ligation—both followed by oxidation in solution phase. Tridegin and truncated analogues were examined for their activity and revealed a particular importance of the C‐terminal region of the parent peptide. Based on these studies a minimal sequence required for factor XIIIa inhibition could be identified. Our data revealed that the glutamine residue at position 52 (Q⁵²) of tridegin most likely binds to the active site of factor XIIIa and was therefore suggested to react with the enzyme. The function of the N‐terminal region is also discussed, as the isolated C‐terminal segment of tridegin lost its inhibitory activity rapidly in the presence of factor XIIIa, whereas this was not the case for the full‐length inhibitor.     

Impact of the addition of dolomite to cream-firing clays on the technological and color properties of sintered ceramics

Sintered ceramics, represented by ceramic tiles or clinker bricks, are widely used in the building materials industry due to their technological properties and visual qualities. The topic of color changing of ceramic materials from cream-firing clays with the use of mineral additives has not been addressed to date. The aim of the paper was to investigate the effect of granulation of dolomite additives to ceramic masses based on cream-firing Borkowice clay on the color and properties of fired ceramic materials. The paper proposes that grain size of mineral additive affects the color of sintered ceramics. In order to confirm this hypothesis, a number of experiments were performed, consisting of determination of the color and technological properties of ceramic materials. The conducted tests showed that the color and technological properties of sintered ceramics are influenced by the grain size of the additives used.