Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.     

New Insights on the Nuclear Functions and Targeting of FAK in Cancer

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed and activated in both adult and pediatric cancers, where it plays important roles in the regulation of pathogenesis and progression of the malignant phenotype. FAK exerts its functions in cancer by two different ways: a kinase activity in the cytoplasm, mainly dependent on the integrin signaling, and a scaffolding activity into the nucleus by networking with different gene expression regulators. For this reason, FAK has to be considered a target with high therapeutic values. Indeed, evidence suggests that FAK targeting could be effective, either alone or in combination, with other already available treatments. Here, we propose an overview of the novel insights about FAK’s structure and nuclear functions, with a special focus on the recent findings concerning the roles of this protein in cancer. Additionally, we provide a recent update on FAK inhibitors that are currently in clinical trials for patients with cancer, and discuss the challenge and future directions of drug-based anti-FAK targeted therapies.     

An alternative encapsulation approach for production of active chitosan–propolis beads

Encapsulation is a promising technology to carry natural active substances, preventing their loss and maintaining their stability until use. Beads of chitosan‐containing propolis have been prepared using a mono‐pore filter device, which permits the encapsulation of natural polyphenols avoiding heat treatments, high shear rates and the use of toxic solvents. Beads proved to be active against Bacillis cereus, Escherichia coli, Listeria innocua, Pseudomonas fluorescens, Yarrovia lipolytica and three moulds strains; the highest effect was found against Staphylococcus aureus (MIC 0.8 mg beads mL^?1). Results in liquid cultures of S. aureus evidenced that beads were able to release the flavonoids from propolis: the diffusion of the active compounds is a key factor in the exploitation of the microbial activity. The obtained chitosan–propolis beads represent an example of natural antimicrobial delivery system that could be used to prevent the growth of pathogenic/spoilage bacteria in food applications.     

Characterization of PLLA scaffolds for biomedical applications

The porosity and pore size distribution of three-dimensional scaffolds have direct implications on their biomedical applications (tissue engineering, drug delivery, and wound dressing). Accordingly, in this paper, a fast, facile, and conservative method relying on low-field nuclear magnetic resonance (LF-NMR) for the evaluation of mean pore size and pore size distribution of polymeric scaffolds is reported. The applicability of the technique is demonstrated on poly-L-lactic acid scaffolds fabricated using the thermal induced phase separation. Results obtained through LF-NMR are successfully compared to scanning electron microscope and X-ray microcomputed tomography micrographs.     

A Decomposition of the Tikhonov Regularization Functional Oriented to Exploit Hybrid Multilevel Parallelism

We introduce a decomposition of the Tikhonov Regularization (TR) functional which split this operator into several TR functionals, suitably modified in order to enforce the matching of their solutions. As a consequence, instead of solving one problem we can solve several problems reproducing the initial one at smaller dimensions. Such approach leads to a reduction of the time complexity of the resulting algorithm. Since the subproblems are solved in parallel, this decomposition also leads to a reduction of the overall execution time. Main outcome of the decomposition is that the parallel algorithm is oriented to exploit the highest performance of parallel architectures where concurrency is implemented both at the coarsest and finest levels of granularity. Performance analysis is discussed in terms of the algorithm and software scalability. Validation is performed on a reference parallel architecture made of a distributed memory multiprocessor and a Graphic Processing Unit. Results are presented on the Data Assimilation problem, for oceanographic models.     

Tuning of level-set speed function for speckled image segmentation

The segmentation of speckled images, as the synthetic aperture radar (SAR) images, is usually recognized as a very complex problem, because of the speckle, multiplicative noise, which produces granular images. In segmentation problems, based on level set method, the evolution of the curve is determined by a speed function, which is fundamental to achieve a good segmentation. In this paper we propose a study of the new speed function obtained by the linear combination of image average intensity and image gradient speed functions. Thus the aim is tuning the combined speed in the segmentation process. We segmented synthetic images by tuning parameters of the new speed function and we evaluated the best computed results. Then we applied this experimental setup to real SAR images, which are PRecision Images, acquired during European Remote Sensing mission, and a Cosmo-SkyMed image. In particular, we are interested in monitoring complex areas with low light covered by clouds, as coastlines and polar regions may be. In Earth Observation, the acquisition of SAR data becomes fundamental, since the SAR sensor can work in the night/day and in all weather conditions.     

Implementation and performance evaluation of a database of chemical formulas for the screening of pharmaco/toxicologically relevant compounds in biological samples using electrospray ionization-time-of-flight mass spectrometry

Electrospray ionization (ESI)-time-of-flight (TOF) MS enables searching a wide number of pharmaco/toxicologically relevant compounds (PTRC) in biosamples. However, the number of identifiable PTRC depends on extension of reference database of chemical formulas/compound names. Previous approaches proposed in-house or commercial databases with limitations either in PTRC number or content (e.g., few metabolites, presence of non-PTRC). In the frame of development of a ESI-TOF PTRC screening procedure, a subset of PubChem Compound as reference database is proposed. Features of this database (approximately 50,500 compounds) are illustrated, and its performance evaluated through analysis by capillary electrophoresis (CE)-ESI-TOF of hair/blood/urine collected from subjects under treatment with known drugs or by comparison with reference standards. The database is rich in parent compounds of pharmaceutical and illicit drugs, pesticides, and poisons and contains many metabolites (including about 6000 phase I metabolites and 180 glucuronides) and related substances (e.g., impurities, esters). The average number of hits with identical chemical formula is 1.82 +/- 2.27 (median = 1, range 1-39). Minor deficiencies, redundancies, and errors have been detected that do not limit the potential of the database in identifying unknown PTRC. The database allows a much broader search for PTRC than other commercial/in-house databases of chemical formulas/compound names previously proposed. However, the probability that a search retrieves different PTRC having identical chemical formula is higher than with smaller databases, and additional information (anamnestic/circumstantial data, concomitant presence of parent drug and metabolite, selective sample preparation, liquid chromatographic retention, and CE migration behavior) must be used in order to focus the search more tightly.     

Structure-Preserving Hierarchical Decompositions

A hierarchy tree of a graph G is a rooted tree whose leaves are the vertices of G; the internal nodes are usually called clusters. Hierarchy trees are well suited for representing hierarchical decompositions of graphs. In this paper we introduce the notion of P-validity of hierarchy trees with respect to a given graph property P. This notion reflects the similarity between any high-level representation of G obtained from the hierarchy tree and the topological structure of G. Maintaining the properties of a graph at any level of abstraction is especially relevant in graph drawing applications. We present a structural characterization of P-valid hierarchy trees when the clustered graph is a tree and property P is the acyclicity. Besides being interesting in its own right, our structure theorem can be used in the design of a polynomial time algorithm for recognizing P-valid hierarchy trees.     

Anti-Müllerian Hormone,Growth Hormone,and Insulin-Like Growth Factor 1 Modulate the Migratory and Secretory Patterns of GnRH Neurons

Anti-Müllerian hormone (AMH) is secreted by Sertoli or granulosa cells. Recent evidence suggests that AMH may play a role in the pathogenesis of hypogonadotropic hypogonadism (HH) and that its serum levels could help to discriminate HH from delayed puberty. Moreover, the growth hormone (GH)/insulin-like growth factor 1 (IGF1) system may be involved in the function of gonadotropin-releasing hormone (GnRH) neurons, as delayed puberty is commonly found in patients with GH deficiency (GHD) or with Laron syndrome, a genetic form of GH resistance. The comprehension of the stimuli enhancing the migration and secretory activity of GnRH neurons might shed light on the causes of delay of puberty or HH. With these premises, we aimed to better clarify the role of the AMH, GH, and IGF1 on GnRH neuron migration and GnRH secretion, by taking advantage of previously established models of immature (GN11 cell line) and mature (GT1-7 cell line) GnRH neurons. Expression of Amhr, Ghr, and Igf1r genes was confirmed in both cell lines. Cells were then incubated with increasing concentrations of AMH (1.5–150 ng/mL), GH (3–1000 ng/mL), or IGF1 (1.5–150 ng/mL). All hormones were able to support GN11 cell chemomigration. AMH, GH, and IGF1 significantly stimulated GnRH secretion by GT1-7 cells after a 90-min incubation. To the best of our knowledge, this is the first study investigating the direct effects of GH and IGF1 in GnRH neuron migration and of GH in the GnRH secreting pattern. Taken together with previous basic and clinical studies, these findings may provide explanatory mechanisms for data, suggesting that AMH and the GH-IGF1 system play a role in HH or the onset of puberty.