Anti-HSV Activity of Metallic Nanoparticles Functionalized with Sulfonates vs. Polyphenols.

Metallic nanoparticles exhibit broad-spectrum activity against bacteria, fungi, and viruses. The antiviral activity of nanoparticles results from the multivalent interactions of nanoparticles with viral surface components, which result from the nanometer size of the material and the presence of functional compounds adsorbed on the nanomaterial surface. A critical step in the virus infection process is docking and entry of the virus into the host cell. This stage of the infection can be influenced by functional nanomaterials that exhibit high affinity to the virus surface and hence can disrupt the infection process. The affinity of the virus to the nanomaterial surface can be tuned by the specific surface functionalization of the nanomaterial. The main purpose of this work was to determine the influence of the ligand type present on nanomaterial on the antiviral properties against herpes simplex virus type 1 and 2. We investigated the metallic nanoparticles (gold and silver) with different sizes (5 nm and 30 nm), coated either with polyphenol (tannic acid) or sulfonates (ligands with terminated sulfonate groups). We found that the antiviral activity of nano-conjugates depends significantly on the ligand type present on the nanoparticle surface.

Lactoferrin-Functionalized Noble Metal Nanoparticles as New Antivirals for HSV-2 Infection.

(1) Background: Lactoferrin has been recognized as a potent inhibitor of human herpetic viruses, such as herpes simplex type 1 (HSV-1) and 2 (HSV-2). In this work, we tested if silver and gold nanoparticles modified with lactoferrin (LF-Ag/AuNPs) can become novel microbicides with additional adjuvant properties to treat genital herpes infection. (2) Methods: The antiviral and cytotoxic activities of LF-Ag/AuNPs were tested in human skin HaCaT and vaginal VK-2-E6/E7 keratinocytes. Viral titers and immune responses after treatment with LF-Ag/AuNPs were tested in murine vaginal HSV-2 infection. (3) Results: LF-Ag/AuNPs inhibited attachment and entry of HSV-2 in human keratinocytes much better than lactoferrin. Furthermore, pretreatment with LF-AgNPs led to protection from infection. Infected mice treated intravaginally with LF-Ag/AuNPs showed lower virus titers in the vaginal tissues and spinal cords in comparison to treatment with lactoferrin. Following treatment, vaginal tissues showed a significant increase in CD8+/granzyme B + T cells, NK cells and dendritic cells in comparison to NaCl-treated group. LF-Ag/AuNPs-treated animals also showed significantly better expression of IFN-γ, CXCL9, CXCL10, and IL-1ß in the vaginal tissues. (4) Conclusions: Our findings show that LF-Ag/AuNPs could become effective novel antiviral microbicides with immune-stimulant properties to be applied upon the mucosal tissues.

New Star-Shaped Polyether-Pentols (PEPOs) for Fabrication of Crosslinked Polyurethanes-Synthesis and Characterization.

Polyether-pentols (PEPOs) were synthesized from glycidyl ethers and butylene oxide with the application of tripotassium salts of 2,2,6,6-tetrakis(hydroxymethyl)cyclohexanol (HMCH) activated 18C6 for ring-opening polymerization (ROP). The construction of the applied initiator system reflects the ability of crown ether to influence the degree of ion-pair separation with an increased activating effect. As a result formation of bi- or trimodal polymers was observed with molar masses in the range of (Mn = 1200-6000). The observed multi-fraction composition is prescribed to the formation of ionic aggregates with different reactivities during polymerization. The mechanism of the studied processes is discussed. The obtained PEPOs served for a crosslinked PUR synthesis, for which the hydrogen bond index for coupling of hard segments was calculated. Additionally, the range of phase separation was calculated that was higher for PUR-containing aromatic rings as the substituent.

Effect of Polythiophene Content on Thermomechanical Properties of Electroconductive Composites.

The thermal, mechanical and electrical properties of polymeric composites combined using polythiophene (PT) dopped by FeCl3 and polyamide 6 (PA), in the aspect of conductive constructive elements for organic solar cells, depend on the molecular structure and morphology of materials as well as the method of preparing the species. This study was focused on disclosing the impact of the polythiophene content on properties of electrospun fibers. The elements for investigation were prepared using electrospinning applying two substrates. The study revealed the impact of the substrate on the conductive properties of composites. In this study composites exhibited good thermal stability, with T5 values in the range of 230-268 °C that increased with increasing PT content. The prepared composites exhibited comparable PA Tg values, which indicates their suitability for processing. Instrumental analysis of polymers and composites was carried out using Fourier Transform Infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and scanning electron microscopy (SEM).

Effect of polyaniline content and protonating dopants on electroconductive composites.

Elastic constructive elements prepared by electrospinning using polyacrylonitrile/polyaniline (PAN/PANI) electroconductive composites were prepared and investigated in terms of their thermal and mechanical properties. This study was focused on the impact of the type of counterion of polyaniline and the PANI content in composites on the thermal, conductive and morphological properties of electrospun fibers. In this study, composites obtained from PANI doped with sulfuric acid showed the highest conductivity, and composites obtained from PANI doped with hydrochloric acid showed the highest thermal stability. All obtained composites exhibited good thermal stability, with T5 values in the range of 230-268 °C that increased with increasing PANI content. The prepared composites exhibited comparable PAN Tg values, which indicates their suitability for processing. Instrumental analysis of polymers and composites was carried out using UV-visible spectroscopy, thermogravimetric analysis, differential scanning calorimetry, dynamic mechanical thermal analysis and scanning electron microscopy.

Discrimination of normal oral mucosa from oral cancer by mass spectrometry imaging of proteins and lipids.

Identification of biomarkers for molecular classification of cancer and for differentiation between cancerous and normal epithelium remains a vital issue in the field of head and neck cancer. Here we aimed to compare the ability of proteome and lipidome components to discriminate oral cancer from normal mucosa. Tissue specimens including squamous cell cancer and normal epithelium were analyzed by MALDI mass spectrometry imaging. Two molecular domains of tissue components were imaged in serial sections-peptides (resulting from trypsin-processed proteins) and lipids (primarily zwitterionic phospholipids), then regions of interest corresponding to cancer and normal epithelium were compared. Heterogeneity of cancer regions was higher than the heterogeneity of normal epithelium, and the distribution of peptide components was more heterogeneous than the distribution of lipid components. Moreover, there were more peptide components than lipid components that showed significantly different abundance between cancer and normal epithelium (median of the Cohen's effect was 0.49 and 0.31 in case of peptide and lipid components, respectively). Multicomponent cancer classifier was tested (vs. normal epithelium) using tissue specimens from three patients and then validated with a tissue specimen from the fourth patient. Peptide-based signature and lipid-based signature allowed cancer classification with a weighted accuracy of 0.85 and 0.69, respectively. Nevertheless, both classifiers had very high precision (0.98 and 0.94, respectively). We concluded that though molecular differences between cancerous and normal mucosa were higher in the proteome domain than in the analyzed lipidome subdomain, imaging of lipidome components also enabled discrimination of oral cancer and normal epithelium. Therefore, both cancer proteome and lipidome are promising sources of biomarkers of oral malignancies.

Discrimination of papillary thyroid cancer from non-cancerous thyroid tissue based on lipid profiling by mass spectrometry imaging.

INTRODUCTION: The distinction of papillary thyroid carcinomas from benign thyroid lesions has important implication for clinical man-agement. Classification based on histopathological features can be supported by molecular biomarkers, including lipidomic signatures, identified with the use of high-throughput mass spectrometry techniques. Formalin fixation is a standard procedure for stabilization and preservation of tissue samples, therefore this type of samples constitute highly valuable source of clinical material for retrospective molecular studies. In this study we used mass spectrometry imaging to detect lipids discriminating papillary cancer from not cancerous thyroid directly in formalin-fixed tissue sections. MATERIAL AND METHODS: For this purpose imaging and profiling of lipids present in non-malignant and cancerous thyroid tissue specimens were conducted. High resolution MALDI-Q-Ion Mobility-TOF-MS technique was used for lipidomic analysis of formalin fixed thyroid tissue samples. Lipids were identified by the comparison of the exact molecular masses and fragmentation pathways of the protonated molecule ions, recorded during the MS/MS experiments, with LIPID MAPS database. RESULTS: Several phosphatidylcholines (32:0, 32:1, 34:1 and 36:3), sphingomyelins (34:1 and 36:1) and phosphatidic acids (36:2 and 36:3) were detected and their abundances were significantly higher in cancerous tissue compared to non-cancerous tissue. The same lipid species were detected in formalin-fixed as in fresh-frozen tissue, but [M + Na]+ ions were the most abundant in formalin fixed whereas [M + K]+ ions were predominant in fresh tissue. CONCLUSIONS: Our results prove the viability of MALDI-MSI for analysis of lipid distribution directly in formalin-fixed tissue, and the potential for their use in the classification of thyroid diseases.

Synthesis, spectroscopic, electrochemical and computational studies of rhenium(i) tricarbonyl complexes based on bidentate-coordinated 2,6-di(thiazol-2-yl)pyridine derivatives.

Nine rhenium(i) complexes possessing three carbonyl groups together with a bidentate coordinated 2,6-di(thiazol-2-yl)pyridine derivative were synthesized to examine the impact of structure modification of the triimine ligand on the photophysical, thermal and electrochemical properties of [ReCl(CO)3(4-Rn-dtpy-κ2N)]. The Re(i) complexes were fully characterized using IR, 1H and 13C, HRMS-ESI and single crystal X-ray analysis. Their thermal properties were evaluated using DSC and TGA measurements. Photoluminescence spectra of [ReCl(CO)3(4-Rn-dtpy-κ2N)] were investigated in solution and in the solid state, at 298 and 77 K. Both emission wavelengths and quantum yields of [ReCl(CO)3(4-Rn-dtpy-κ2N)] were found to be structure-related, demonstrating a crucial role of the substituent attached to the 2,6-di(thiazol-2-yl)pyridine skeleton. In order to fully understand the photophysical properties of [ReCl(CO)3(4-Rn-dtpy-κ2N)], density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were performed. Furthermore, the complexes which showed appropriate solubility in chloroform were tested as an emissive active layer in OLED devices.

Photocatalytic ozonation using doped TiO2 catalysts for the removal of parabens in water.

Conventional wastewater treatments are inefficient for the removal of parabens. The aim of this study was finding a suitable solution using ozone and UVA irradiation combined with TiO2 catalysts doped with different noble metals (Ag, Pt, Pd, Au). Photocatalytic ozonation required lower amounts of ozone for higher efficiency on the removal of parabens, chemical oxygen demand (COD) and total organic carbon (TOC). The best catalyst for the initial contaminants degradation was 0.5% Ag-TiO2 leading to total parabens removal using 46mgO3/L. Due to the relative low mineralization achieved, the toxicity of the treated solutions was still compared with the initial one over several species (Vibrio fischeri, Lepidium sativum and Corbicula fluminea). All the treatments applied led to a clear decrease on the toxicity compared with initial mixture of parabens. From an economical point of view, it was concluded that the presence of UVA irradiation increased the energy consumption compared with catalytic ozonation with these catalysts but it can decrease the time of reaction. From the by-products analysis, it was concluded that hydroxylation appears to be the most significant reaction pathway and the main responsible for parabens degradation.

Polypeptide components of oligomeric legumin-like thiamin-binding protein from buckwheat seeds characterized by partial amino acid sequencing and photoaffinity labeling.

Among thiamin-binding proteins that ubiquitously occur in plant seeds, that of common buckwheat became a model of extensive studies of the chemical mechanism of ligand-protein interaction. In this work, the polypeptide components of buckwheat seed thiamin-binding protein (BSTBP) are identified and characterized. We suggest that BSTBP is probably a fraction of major storage 13 S globulin (legumin), has an average molecular mass of 235 kDa and comprises hexamers of 57-kDa and 38-kDa subunits in variable combinations. Each subunit is a pair of disulfide-linked polypeptide chains, 36 kDa plus 24 kDa and two-times 22 kDa, respectively. The N-terminal sequences of 22-kDa and 24-kDa components show strict homology with those reported for "basic subunits" of buckwheat legumin. By photoaffinity labeling of BSTBP with 4-azido-2-nitrobenzoylthiamine, it is shown that the 36-kDa chain plays the major role in thiamin binding, but the other chains may also be variably involved. Putative thiamin-binding fragments are identified and sequenced.