Increased in vitro Anti-HIV Activity of Caffeinium-Functionalized Polyoxometalates

Polyoxometalates (POMs), molecular metal oxide anions, are inorganic clusters with promising antiviral activity. Herein we report increased anti-HIV-1 activity of a POM when electrostatically combined with organic counter-cations. To this end, Keggin-type cerium tungstate POMs have been combined with organic methyl-caffeinium (Caf) cations, and their cytotoxicity, antiviral activity and mode of action have been studied. The novel compound, Caf₄K[β₂-CeSiW₁₁O₃₉]×H₂O, exhibits sub-nanomolar antiviral activity and inhibits HIV-1 infectivity by acting on an early step of the viral infection cycle. This work demonstrates that combination of POM anions and organic bioactive cations can be a powerful new strategy to increase antiviral activity of these inorganic compounds.     

Mediator-Related Symptoms and Anaphylaxis in Children with Mastocytosis

Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier’s sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.     

Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D₃ metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)₂D₃ analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.     

CR composites with improved processing safety crosslinked via Heck's reaction

The aim of this study was to optimize the composition of the chloroprene rubber (CR) composites crosslinked via the Heck-type reaction to ensure their safe processing at elevated temperature. The developed curing system consisting of iron (III) acetylacetonate (Fe(acac)) and triethanolamine (TEOA) demonstrates high activity and more eco-friendly composition in comparison with metal oxide system, commercially used for CR crosslinking. However, the high activity of Fe(acac)/TEOA system results in a short scorch time, which is the greatest disadvantage regarding the safe processing of CR rubber and thus, must be improved. Therefore, CR compounds with Fe(acac) in the presence of different additives were studied. The longest scorch times (t₀₂) were observed for rubber compounds with urotropine (U), N-cyclohexyl-2-benzothiazole sulfenamide (CBS) or salicylic acid. Moreover, vulcanizates containing these additives exhibited higher tensile strengths and elongation at breaks compared to CR crosslinked with Fe(acac)/TEOA system.     

Corrosion of structural constituents of 2017 aluminium alloy in acidic solutions containing inhibitors

The objective of this study is to establish the corrosion behaviour of the most important structural constituents of the aluminium alloy 2017 in orthophosphoric acid solutions containing heteropolyoxomolybdate, tungstate and vanadate. These are potential candidates for replacing toxic hexavalent chromium species in stripping solution for anodic coatings. The corrosion rate of the alloy is estimated with linear polarisation method. It decreases from 0.58 mA cm⁻² in uninhibited solution to 0.10 mA cm⁻² in a solution containing heteropolyoxomolybdate species. Microscopic studies reveal that heteropolyoxomolybdate species inhibit corrosion of the matrix and intermetallic Al₁₅(Fe,Mn)₃(Si,Cu)₂ but not Mg₂Si. Intermetallic Al₂Cu remains not corroded. Heteropolyoxotungstate species virtually do not inhibit the corrosion of the alloy. The solution containing vanadium species is not stable with time and the corrosion rate is not determined. Nevertheless, corrosion of the matrix is inhibited, but intermetallics Al₁₅(Fe,Mn)₃(Si,Cu)₂ together with Mg₂Si are dissolved. X-ray photoelectron spectroscopy is used for examination of a corrosion product precipitated on the surface.     

Impact of chloride on the mineralogy of hydrated Portland cement systems

Chloride ion is in part bound into ordinary Portland cement paste and modifies its mineralogy. To understand this a literature review of its impacts has been made and new experimental data were obtained. Phase pure preparations of Friedel's salt, Ca₄Al₂(Cl)_1.95(OH)_12.05·4H₂O, and Kuzel's salt, Ca₄Al₂(Cl)(SO₄)_0.5(OH)₁₂·6H₂O, were synthesized and their solubilities were measured at 5, 25, 55 and 85 °C. After equilibration, solid phases were analysed by X-ray diffraction while the aqueous solutions were analysed by atomic absorption spectroscopy and ion chromatography. The solid solutions and interactions of Friedel's salt with other AFm phases were determined at 25 °C experimentally and by calculations. In hydrated cements, anion sites in AFm are potentially occupied by OH, SO₄ and CO₃ ions whereas Cl may be introduced under service conditions. Chloride readily displaces hydroxide, sulfate and carbonate in the AFm structures. A comprehensive picture of phase relations of AFm phases and their binding capacity for chloride is provided for pH ∼ 12 and 25 °C. The role of chloride in AFt formation and its relevance to corrosion of embedded steel are discussed in terms of calculated aqueous [Cl⁻]/[OH⁻] molar ratios.     

Combined Protein and Alkaloid Research of Chelidonium majus Latex Reveals CmMLP1 Accompanied by Alkaloids with Cytotoxic Potential to Human Cervical Carcinoma Cells

Chelidonium majus L. is a latex-bearing plant used in traditional folk medicine to treat human papillomavirus (HPV)-caused warts, papillae, and condylomas. Its latex and extracts are rich in many low-molecular compounds and proteins, but there is little or no information on their potential interaction. We describe the isolation and identification of a novel major latex protein (CmMLP1) composed of 147 amino acids and present a model of its structure containing a conserved hydrophobic cavity with high affinity to berberine, 8-hydroxycheleritrine, and dihydroberberine. CmMLP1 and the accompanying three alkaloids were present in the eluted chromatographic fractions of latex. They decreased in vitro viability of human cervical cancer cells (HPV-negative and HPV-positive). We combined, for the first time, research on macromolecular and low-molecular-weight compounds of latex-bearing plants in contrast to other studies that investigated proteins and alkaloids separately. The observed interaction between latex protein and alkaloids may influence our knowledge on plant defense. The proposed toolbox may help in further understanding of plant disease resistance and in pharmacological research.     

Cationic Phenosafranin Photosensitizers Based on Polyhedral Oligomeric Silsesquioxanes for Inactivation of Gram-Positive and Gram-Negative Bacteria

The high photodynamic effect of the Newman strain of the S. aureus and of clinical strains of S. aureus MRSA 12673 and E. coli 12519 are observed for new cationic light-activated phenosafranin polyhedral oligomeric silsesquioxane (POSS) conjugates in vitro. Killing of bacteria was achieved at low concentrations of silsesquioxanes (0.38 µM) after light irradiation (λ_{em. max} = 522 nm, 10.6 mW/cm²) for 5 min. Water-soluble POSS-photosensitizers are synthesized by chemically coupling a phenosafranin dye (PSF) (3,7-diamino-5-phenylphenazine chloride) to an inorganic silsesquioxane cage activated by attachment of succinic anhydride rings. The chemical structure of conjugates is confirmed by ¹H, ¹³C NMR, HRMS, IR, fluorescence spectroscopy and UV-VIS analyzes. The APDI and daunorubicin (DAU) synergy is investigated for POSSPSFDAU conjugates. Confocal microscopy experiments indicate a site of intracellular accumulation of the POSSPSF, whereas iBuPOSSPSF and POSSPSFDAU accumulate in the cell wall or cell membrane. Results from the TEM study show ruptured S. aureus cells with leaking cytosolic mass and distorted cells of E. coli. Bacterial cells are eradicated by ROS produced upon irradiation of the covalent conjugates that can kill the bacteria by destruction of cellular membranes, intracellular proteins and DNA through the oxidative damage of bacteria.     

Structural Studies of the Lipopolysaccharide of Aeromonas veronii bv. sobria Strain K133 Which Represents New Provisional Serogroup PGO1 Prevailing among Mesophilic Aeromonads on Polish Fish Farms

In the present work, we performed immunochemical studies of LPS, especially the O-specific polysaccharide (O-PS) of Aeromonas veronii bv. sobria strain K133, which was isolated from the kidney of carp (Cyprinus carpio L.) during an outbreak of motile aeromonad infection/motile aeromonad septicemia (MAI/MAS) on a Polish fish farm. The structural characterization of the O-PS, which was obtained by mild acid degradation of the LPS, was performed with chemical methods, MALDI-TOF mass spectrometry, and ¹H and ¹³C NMR spectroscopy. It was revealed that the O-PS has a unique composition of a linear tetrasaccharide repeating unit and contains a rarely occurring sugar 2,4-diamino-2,4,6-trideoxy-D-glucose (bacillosamine), which may determine the specificity of the serogroup. Western blotting and ELISA confirmed that A. veronii bv. sobria strain K133 belongs to the new serogroup PGO1, which is one of the most commonly represented immunotypes among carp and trout isolates of Aeromonas sp. in Polish aquacultures. Considering the increase in the MAI/MAS incidences and their impact on freshwater species, also with economic importance, and in the absence of an effective immunoprophylaxis, studies of the Aeromonas O-antigens are relevant in the light of epidemiological data and monitoring emergent pathogens representing unknown antigenic variants and serotypes.     

Xanthohumol for Human Malignancies: Chemistry,Pharmacokinetics and Molecular Targets

Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of Humulus lupulus L. (Hop plant). XH is an important ingredient in beer and is considered a significant bioactive agent due to its diverse medicinal applications, which include anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, antiviral, antifungal, antigenotoxic, antiangiogenic, and antimalarial effects as well as strong anticancer activity towards various types of cancer cells. XH acts as a wide ranging chemopreventive and anticancer agent, and its isomer, 8-prenylnaringenin, is a phytoestrogen with strong estrogenic activity. The present review focuses on the bioactivity of XH on various types of cancers and its pharmacokinetics. In this paper, we first highlight, in brief, the history and use of hops and then the chemistry and structure–activity relationship of XH. Lastly, we focus on its prominent effects and mechanisms of action on various cancers and its possible use in cancer prevention and treatment. Considering the limited number of available reviews on this subject, our goal is to provide a complete and detailed understanding of the anticancer effects of XH against different cancers.