Pro-inflammatory Signaling in a 3D Organotypic Skin Model after Low LET Irradiation-NF-kappa B, COX-2 Activation, and Impact on Cell Differentiation

Nearly 85% of radiotherapy patients develop acute radiation dermatitis, which is an inflammatory reaction of the skin at the treatment field and in the surrounding area. The aims of this study were to unravel the mechanisms of radiation-induced inflammatory responses after localized irradiation in a human 3D organotypic skin culture model. This could provide possible inflammatory targets for reduction of skin side effects. 3D organotypic skin cultures were set up and locally irradiated with 225 kVp X-rays, using a combination of full exposure and partial shielding (50%) of the cultures. The secretion of pro-inflammatory cytokines, the phenotype, and the differentiation markers expression of the cultures were assessed up to 10 days postirradiation. The pro-inflammatory transcription factor nuclear factor kappa B (NF-kappa B) and cyclooxygenase-2 (COX-2) pathways have been studied. The results showed fast activation of NF-kappa B, most likely triggered by DNA damage in the irradiated cells, followed by upregulation of p38 MAPK and COX-2 in the irradiated and surrounding, non-irradiated, areas of the 3D cultures. The application of the COX-2 inhibitor sc-236 was effective at reducing the COX-2 mRNA levels 4 h postirradiation. The same inhibitor also suppressed the PGE2 secretion significantly 72 h after the treatment. The expression of a pro-inflammatory phenotype and abnormal differentiation markers of the cultures were also reduced. However, the use of an NF-kappa B inhibitor (Bay 11-7085) did not have the predicted positive effect on the cultures phenotype postirradiation. Radiation-induced pro-inflammatory responses have been observed in the 3D skin model. The activated signaling pathways involved NF-kappa B transcription factor and its downstream target COX-2. Further experiments aiming to suppress the inflammatory response via specific inhibitors showed that COX-2 is a suitable target for reduction of the normal skin inflammatory responses at radiotherapy, while NF-kappa B inhibition had detrimental effects on the 3D skin model development.Peer reviewe

Use of fermented hemp, chickpea and milling by-products to improve the nutritional value of semolina pasta

A biotechnological approach including enzymatic treatment (protease and xylanase) and lactic acid bacteria fermentation has been evaluated to enhance the nutritional value of semolina pasta enriched with hemp, chickpea and milling by-products. The intense (up to circa, (ca.) 70%) decrease in the peptide profile area and (up to two-fold) increase in total free amino acids, compared to the untreated raw materials, highlighted the potential of lactic acid bacteria to positively affect their in vitro protein digestibility. Fermented and unfermented ingredients have been characterized and used to fortify pasta made under pilot-plant scale. Due to the high contents of protein (ca. 13%) and fiber (ca. 6%) and according to the Regulation of the European Community (EC) No. 1924/2006 fortified pasta can be labelled as a "source of fiber" and a "source of protein". The use of non-wheat flours increased the content of anti-nutritional factors as compared to the control pasta. Nevertheless, fermentation with lactic acid bacteria led to significant decreases in condensed tannins (ca. 50%), phytic acid and raffinose (ca. ten-fold) contents as compared to the unfermented pasta. Moreover, total free amino acids and in vitro protein digestibility values were 60% and 70%, respectively, higher than pasta made only with semolina. Sensory analysis highlighted a strong effect of the fortification on the sensory profile of pasta

Extension of the Shelf-Life of Fresh Pasta Using Chickpea Flour Fermented with Selected Lactic Acid Bacteria

Fresh pasta is subjected to rapid spoilage, mainly due to the metabolic activity of bacteria, yeasts, and especially molds, which negatively affect the sensorial characteristics and the safety of the product. In this work, chickpea flour was fermented with selected lactic acid bacteria, characterized in terms of the antifungal activity, and used to fortify fresh semolina pasta. Pasta was characterized and subjected to a long period of storage after being artificially inoculated with Penicillium roqueforti. Conventional fresh semolina pasta, produced with or without calcium propionate addition, was used as a reference. The water/salt-soluble extract from chickpea sourdough exhibited antifungal activity towards a large spectrum of molds. Its purification led to the identification of ten potentially active peptides. Besides the high content of dietary fibers (4.37%) and proteins (11.20%), nutritional improvements, such as the decrease of the antinutritional factors concentration and the starch hydrolysis index (25% lower than the control) and the increase of the protein digestibility (36% higher than the control), were achieved in fresh pasta fortified with the chickpea sourdough. Inhibition of the indicator mold growth during a 40-day storage period was more effective than in pasta added to calcium propionate

Extension of the shelf-life of fresh pasta using chickpea flour fermented with selected lactic acid bacteria

Fresh pasta is subjected to rapid spoilage, mainly due to the metabolic activity of bacteria, yeasts, and especially molds, which negatively affect the sensorial characteristics and the safety of the product. In this work, chickpea flour was fermented with selected lactic acid bacteria, characterized in terms of the antifungal activity, and used to fortify fresh semolina pasta. Pasta was characterized and subjected to a long period of storage after being artificially inoculated with Penicillium roqueforti. Conventional fresh semolina pasta, produced with or without calcium propionate addition, was used as a reference. The water/salt-soluble extract from chickpea sourdough exhibited antifungal activity towards a large spectrum of molds. Its purification led to the identification of ten potentially active peptides. Besides the high content of dietary fibers (4.37%) and proteins (11.20%), nutritional improvements, such as the decrease of the antinutritional factors concentration and the starch hydrolysis index (25% lower than the control) and the increase of the protein digestibility (36% higher than the control), were achieved in fresh pasta fortified with the chickpea sourdough. Inhibition of the indicator mold growth during a 40-day storage period was more effective than in pasta added to calcium propionate

Relating Trait Variation to Species and Community Productivity in Contrasting Oro-Mediterranean Pastures: A 7-Years Study in the Pollino National Park (S-Italy)

Understanding how functional traits influence community assemblage and functioning is crucial for assessing the effects of global change on vegetation composition. We studied the functional composition (i.e., plant size (SIZE), leaf area (LA), specific leaf area (SLA), and leaf dry matter content (LDMC)) of a xerophile pasture and a mesophile grassland in southern Italy, and recorded species richness (SR), plant cover (COV) and flowering rates (FLOW) over a 7-year period. Both communities revealed the dominance of stress-tolerators, probably reflecting an adaptation to the Mediterranean climate. The functional classification of species distinguished three groups. Species from the mesophile community had larger SIZE and LA, while those from the xerophile pasture showed higher LDMC; SLA was not connected to the source community. Community-level analyses confirmed such patterns, but with higher SLA in the mesophile grassland. While SR was comparable, COV and FLOW varied between the communities. At the species level, LDMC was positively related to FLOW and the inter-annual variability of COV and FLOW. At the community level, SIZE, LA and SLA were positively related to COV, while LDMC was positively related to FLOW. Trait variations can significantly contribute to the xerophile-mesophile shift in Mediterranean mountain vegetation, by regulating the productivity of species and communities in the two contexts and, possibly, their responsiveness to global change

Biological Mechanisms of Gold Nanoparticle Radiosenstitisation

There has been growing interest in the use of nanomaterials for a range of biomedical applications over the last number of years. In particular, gold nanoparticles (GNPs) possess a number of unique properties that make them ideal candidates as radiosensitizers on the basis of their strong photoelectric absorption coefficient and ease of synthesis. However, despite promising preclinical evidence in vitro supported by a limited amount of in vivo experiments, along with advances in mechanistic understanding, GNPs have not yet translated into the clinic. This may be due to disparity between predicted levels of radiosensitization based on physical action, observed biological response and an incomplete mechanistic understanding, alongside current experimental limitations. This paper provides a review of the current state of the field, highlighting the potential underlying biological mechanisms in GNP radiosensitization and examining the barriers to clinical translation

Characterization of Inorganic Scintillator Detectors for Dosimetry in Image-Guided Small Animal Radiotherapy Platforms

The purpose of the study was to characterize a detection system based on inorganic scintillators and determine its suitability for dosimetry in preclinical radiation research. Dose rate, linearity, and repeatability of the response (among others) were assessed for medium-energy X-ray beam qualities. The response's variation with temperature and beam angle incidence was also evaluated. Absorbed dose quality-dependent calibration coefficients, based on a cross-calibration against air kerma secondary standard ionization chambers, were determined. Relative output factors (ROF) for small, collimated fields (≤10 mm × 10 mm) were measured and compared with Gafchromic film and to a CMOS imaging sensor. Independently of the beam quality, the scintillator signal repeatability was adequate and linear with dose. Compared with EBT3 films and CMOS, ROF was within 5% (except for smaller circular fields). We demonstrated that when the detector is cross-calibrated in the user's beam, it is a useful tool for dosimetry in medium-energy X-rays with small fields delivered by Image-Guided Small Animal Radiotherapy Platforms. It supports the development of procedures for independent "live" dose verification of complex preclinical radiotherapy plans with the possibility to insert the detectors in phantoms

PV reconfiguration systems: A technical and economic study

Dynamical electrical array reconfiguration strategies for grid-connected PV systems have been proposed as solution to improve energy production due to the mismatch effect of PV plants during partial shading conditions. Strategies are based on the use of dynamic connections between PV panels given by the employment of switches that allow for each panel the series, parallel or exclusion connections, physically changing the electrical connections between the related PV modules, consequentially modifying the layout of the plant. Usually the cost of the dynamic matrix is not taken into account. This novel work evaluates the economic advantages obtained by the use of reconfiguration strategies in PV systems, by taking into consideration the price of energy due to incentives in different European and non-European countries and correlates it with the employment of two types of reconfigurators, with different internal structures. For each of the incentives proposed by the different Countries, the main strength and weakness points of the possible investment are highlighted and critically analyzed. From this analysis, it can be stated that the adoption of reconfiguration systems, in certain cases, can be a very convenient solution

Experimental investigation on the performances of a multilevel inverter using a field programmable gate array-based control system

The Field Programmable Gate Array (FPGA) represents a valid solution for the design of control systems for inverters adopted in many industry applications, because of both its high flexibility of use and its high-performance with respect to other types of digital controllers. In this context, this paper presents an experimental investigation on the harmonic content of the voltages produced by a three-phase, five level cascaded H-Bridge Multilevel inverter with an FPGA-based control board, aiming also to evaluate the performance of the FPGA through the implementation of the main common modulation techniques and the comparison between simulation and experimental results. The control algorithms are implemented by means of the VHDL programming language. The output voltage waveforms, which have been obtained by applying to the inverter the main PWM techniques, are compared in terms of THD%. Simulation and experimental results are analyzed, compared and finally discussed