Assessment of Growth Factors,Cytokines, and Cellular Markers in Saliva of Patients with Trigeminal Neuralgia

We proposed to perform a comparative analysis of growth factors, cytokines, and chemokine receptors on the salivary cells in the saliva obtained from trigeminal neuralgia (TN) and normal subjects. Saliva was collected from TN and healthy subjects. Salivary cells were isolated by centrifugation. The expression of the cell surface marker was analyzed by flow cytometry. A cytometric bead array was done to measure the levels of cytokines and growth factors on the flow cytometer. Saliva from TN subjects showed lower growth factor levels of Angiopoietin-2, bFGF, HGF, SCF, TGF-α, and VEGF and higher cytokine levels of IL-1β, TNF-α, CCL2, IL-17A, IL-6, and CXCL8, as well as higher expression levels of chemokine receptors CCR1 (CD191), CR3 (CD11b), CCR2 (CD192), CXCR5 (CD185), and CCR5 (CD196) in the cells from TN saliva. A certain set of cytokines and growth factors in the saliva, as well as chemokine receptors on salivary cells, could be a useful tool in the diagnostics and prognostics of trigeminal neuralgia. Trigeminal neuralgia is one of the significant pathological conditions in the class of chronic diseases around the world. Many targeted approaches are being tried by various research groups to utilize the information of the inflammatory microenvironment to resolve the pathology of chronic TN.     

Design and Synthesis of Hsp90 Inhibitors with B-Raf and PDHK1 Multi-Target Activity

The design of multi-target ligands has become an innovative approach for the identification of effective therapeutic treatments against complex diseases, such as cancer. Recent studies have demonstrated that the combined inhibition of Hsp90 and B-Raf provides synergistic effects against several types of cancers. Moreover, it has been reported that PDHK1, which presents an ATP-binding pocket similar to that of Hsp90, plays an important role in tumor initiation, maintenance and progression, participating also to the senescence process induced by B-Raf oncogenic proteins. Based on these premises, the simultaneous inhibition of these targets may provide several benefits for the treatment of cancer. In this work, we set up a design strategy including the assembly and integration of molecular fragments known to be important for binding to the Hsp90, PDHK1 and B-Raf targets, aided by molecular docking for the selection of a set of compounds potentially able to exert Hsp90-B-Raf-PDHK1 multi-target activities. The designed compounds were synthesized and experimentally validated in vitro. According to the in vitro assays, compounds 4 a , 4 d and 4 e potently inhibited Hsp90 and moderately inhibited the PDHK1 kinase. Finally, molecular dynamics simulations were performed to provide further insights into the structural basis of their multi-target activity.     

Ultrasensitive Direct Quantification of Nucleobase Modifications in DNA by Surface‐Enhanced Raman Scattering: The Case of Cytosine

Recognition of chemical modifications in canonical nucleobases of nucleic acids is of key importance since such modified variants act as different genetic encoders, introducing variability in the biological information contained in DNA. Herein, we demonstrate the feasibility of direct SERS in combination with chemometrics and microfluidics for the identification and relative quantification of 4 different cytosine modifications in both single‐ and double‐stranded DNA. The minute amount of DNA required per measurement, in the sub‐nanogram regime, removes the necessity of pre‐amplification or enrichment steps (which are also potential sources of artificial DNA damages). These findings show great potentials for the development of fast, low‐cost and high‐throughput screening analytical devices capable of detecting known and unknown modifications in nucleic acids (DNA and RNA) opening new windows of activity in several fields such as biology, medicine and forensic sciences.     

Metal‐Free Ammonia–Borane Dehydrogenation Catalyzed by a Bis(borane) Lewis Acid

The storage of energy in a safe and environmentally benign way is one of the main challenges of today’s society. Ammonia–borane (AB=NH₃BH₃) has been proposed as a possible candidate for the chemical storage of hydrogen. However, the efficient release of hydrogen is still an active field of research. Herein, we present a metal‐free bis(borane) Lewis acid catalyst that promotes the evolution of up to 2.5 equivalents of H₂ per AB molecule. The catalyst can be reused multiple times without loss of activity. The moderate temperature of 60 °C allows for controlling the supply of H₂ on demand simply by heating and cooling. Mechanistic studies give preliminary insights into the kinetics and mechanism of the catalytic reaction.     

Effect of biotic and abiotic stresses on volatile emission of Achillea collina Becker ex Rchb

This study describes the application of headspace solid-phase microextraction (HS-SPME)–gas chromatography/mass spectrometry (GC/MS) to characterise the volatile fingerprint changes of Achillea collina, induced by aphids' infestation, mechanical damage and jasmonic acid (JA) treatment. The volatile organic compound profiles of A. collina, Prunus persica and Pisum sativum infested by Myzus persicae were also compared. Several changes were observed between control, infested, mechanically damaged and JA-treated plants, and new inducible volatile organic compounds (IVOCs) were emitted in response to biotic or abiotic stresses. Some of these were in common for all stresses and other compounds were in common only for two types of stress. Conversely some IVOCs were emitted only in response to the specific stimuli. The results suggested that there were species-specific and common IVOCs emitted by A. collina, P. persica and P. sativum in response to M. persicae infestation. In conclusion, HS-SPME–GC/MS seems to be a reliable analytical approach to study in vivo plant reaction to external stimuli.     

Assessment of the Antioxidant Capacity of Standard Compounds and Fruit Juices by a Newly Developed Electrochemical Method: Comparative Study with Results from Other Analytical Methods

The antioxidant capacity (AOC) of some standard compounds and commercial beverages was determined using an electroanalytical method which measures the OH radical scavenging ability (OH‐RSC). It is based on the degradation of a thin polyphenol film electrodeposited on glassy carbon following the attack by OH radicals produced by hydrogen peroxide photolysis. The degradation is prevented in presence of increasing concentrations of antioxidants. The same samples were also analyzed by DPPH, ABTS, and ORAC assays. The OH‐RSC method provided AOC values highly correlated with those resulting from the application of ORAC assay for both juices (R=0.90) and standard antioxidants (R=0.96).     

Structural evolution during evaporation of a 3-glycidoxypropyltrimethoxysilane film studied in situ by time resolved infrared spectroscopy

Time resolved infrared spectroscopy has been applied to study in situ the evaporation process of a 3-glycidoxypropyltrimethoxysilane hybrid sol by casting a droplet on a ZnSe substrate; the analysis has been performed in the middle-infrared range and in the near-infrared range. The experiment has allowed following the structural changes induced by water evaporation and the formation of ordered structures within the cast film; the CH(2) scissoring bands have been used as a fingerprint for the disorder to order transition of the hybrid. The experiment has been done using both a fresh sol and an aged sol which produce respectively an amorphous material and a crystalline hybrid material. The analysis has shown that the epoxy groups do not react during the evaporation while the silica structure shows only a slight condensation and an increase in open cage-like species. At the end of evaporation the hybrid has a "soft-like" state which allows structural rearrangements to self-order.     

Artificial neural network combined with principal component analysis for resolution of complex pharmaceutical formulations

A chemometric approach based on the combined use of the principal component analysis (PCA) and artificial neural network (ANN) was developed for the multicomponent determination of caffeine (CAF), mepyramine (MEP), phenylpropanolamine (PPA) and pheniramine (PNA) in their pharmaceutical preparations without any chemical separation. The predictive ability of the ANN method was compared with the classical linear regression method Partial Least Squares 2 (PLS2). The UV spectral data between 220 and 300 nm of a training set of sixteen quaternary mixtures were processed by PCA to reduce the dimensions of input data and eliminate the noise coming from instrumentation. Several spectral ranges and different numbers of principal components (PCs) were tested to find the PCA-ANN and PLS2 models reaching the best determination results. A two layer ANN, using the first four PCs, was used with log-sigmoid transfer function in first hidden layer and linear transfer function in output layer. Standard error of prediction (SEP) was adopted to assess the predictive accuracy of the models when subjected to external validation. PCA-ANN showed better prediction ability in the determination of PPA and PNA in synthetic samples with added excipients and pharmaceutical formulations. Since both components are characterized by low absorptivity, the better performance of PCA-ANN was ascribed to the ability in considering all non-linear information from noise or interfering excipients.     

Oligonuclear ferrocene amides: mixed-valent peptides and potential redox-switchable foldamers

Trinuclear ferrocene tris-amides were synthesized from an Fmoc- or Boc-protected ferrocene amino acid, and hydrogen-bonded zigzag conformations were determined by NMR spectroscopy, molecular modelling, and X-ray diffraction. In these ordered secondary structures orientation of the individual amide dipole moments approximately in the same direction results in a macrodipole moment similar to that of α-helices composed of α-amino acids. Unlike ordinary α-amino acids, the building blocks in these ferrocene amides with defined secondary structure can be sequentially oxidized to mono-, di-, and trications. Singly and doubly charged mixed-valent cations were probed experimentally by Vis/NIR, paramagnetic 1H NMR and M?ssbauer spectroscopy and investigated theoretically by DFT calculations. According to the appearance of intervalence charge transfer (IVCT) bands in solution, the ferrocene/ferrocenium amides are described as Robin-Day class II mixed-valent systems. M?ssbauer spectroscopy indicates trapped valences in the solid state. The secondary structure of trinuclear ferrocene tris-amides remains intact (coiled form) upon oxidation to mono- and dications according to DFT calculations, while oxidation to the trication should break the intramolecular hydrogen bonding and unfold the ferrocene peptide (uncoiled form).     

Green and blue electrochemically generated chemiluminescence from click chemistry--customizable iridium complexes

Cationic cyclometalated iridium complexes containing two anionic phenylpyridine (ppy) ligands and the neutral bidentate triazole-pyridine ligand, 2-(1-substituted-1H-1,2,3-triazol-4-yl)pyridine (pytl), were investigated. The complexes display a rich and reversible electrochemical behavior, upon investigations by cyclic voltammetry in strictly aprotic conditions, that couples with excellent emission quantum yields and long lifetimes of the excited states. Therefore, in organic media, all complexes have generated intense green electrochemiluminescence (ECL) through the so-called annihilation procedure and, importantly, a modulation of the emission energy (to blue) has been easily obtained by simple fluorination of the ppy ligand. Finally, taking advantage of their remarkable solubility in water, intense ECL was also obtained from aqueous buffer solutions using the co-reactant method, thus making all the investigated complexes highly promising for their effective use as ECL labels in bioanalytical applications.