Adequacy of protein and calorie delivery according to the expected calculated targets: a day-by-day assessment in critically ill patients undergoing enteral feeding.

BACKGROUND: In critically ill patients requiring mechanical ventilation for longer than 48-72 h enteral nutrition (EN) should be started early. Because EN alone may be unable to reach the target nutritional requirement, supplemental parenteral nutrition (PN) should be administered. This study aimed at describing the daily rate of administered calories and proteins according to the expected calculated targets. The impact of calorie adequacy, deficit or excess on relevant clinical outcomes was explored. METHODS: A retrospective cohort study was conducted in 217 patients undergoing cardiac surgery, admitted postoperatively in intensive care unit and undergoing EN. The effective intake provided via EN, PN, oral nutritional supplements (ONS) and nonnutritional calories (NNC) was documented for a maximum of 20 days. The administered/required calorie and protein ratios (KcalA/R , ProtA/R ) were calculated daily. Patients receiving 80%-100%, <80% or >100% of KcalA/R and ProtA/R were identified. The association between mean KcalA/R between days 4-7 and 30 days' mortality was explored. RESULTS: A mean KcalA/R ratio of 92.0 ± 40.6% was ensured between days 4 and 20. During days 4-7 the 80%-100% calorie target was achieved in 26.9% of patients, whereas 44.9% were below and 28.2% over this range. EN contributed 47.1% and PN 41.2% to the total energy intake. An increase in 30-day mortality risk was documented for patients exceeding 100% of KcalA/R ratio (adjusted-hazard ratio [HR] 5.2; 95% confidence interval [CI] 1.1 -23.9; p = 0.035). CONCLUSIONS: Despite a preliminary estimate of nutritional requirement, a steady daily optimal 80%-100% KcalA/R was not ensured for all patients. EN contributed only partially to both energy and protein intakes so that PN was largely used to achieve the desired nutritional targets.

Cytotoxicity Profiles and Neuroprotective Properties of the Novel Ifenprodil Analogues as Sigma Ligands.

Neurodegeneration is a slow and progressive loss of neuronal cells or their function in specific regions of the brain or in the peripheral system. Among several causes responsible for the most common neurodegenerative diseases (NDDs), cholinergic/dopaminergic pathways, but also some endogenous receptors, are often involved. In this context, sigma 1 receptor (S1R) modulators can be used as neuroprotective and antiamnesic agents. Herein, we describe the identification of novel S1R ligands endowed with antioxidant properties, potentially useful as neuroprotective agents. We also computationally assessed how the most promising compounds might interact with the S1R protein's binding sites. The in silico predicted ADME properties suggested that they could be able to cross the brain-blood-barrier (BBB), and to reach the targets. Finally, the observation that at least two novel ifenprodil analogues (5d and 5i) induce an increase of the mRNA levels of the antioxidant NRF2 and SOD1 genes in SH-SY5Y cells suggests that they might be effective agents for protecting neurons against oxidative damage.

Oleocanthal Quantification Using 1H NMR Spectroscopy and Polyphenols HPLC Analysis of Olive Oil from the Bianchera/Belica Cultivar.

The cultivar Bianchera is an autochthonous variety from the eastern part of northern Italy, but it is also cultivated in the Slovenian and Croatian peninsula of Istria where it is named Belica (Slovenia) and Bjelica (Croatia). The properties of oleocanthal, a natural anti-inflammatory ibuprofen-like compound found in commercial monocultivar extra virgin olive oils, were determined by means of both quantitative 1H NMR (qNMR) and HPLC analyses, where qNMR was identified as a rapid and reliable method for determining the oleocanthal content. The total phenolic content (TPC) was determined by means of the Folin-Ciocalteau method and the major phenols present in the olive oils were also quantified by means of HPLC analyses. All these analyses confirmed that the cultivar Bianchera was very rich in polyphenols and satisfied the health claim provided by the EU Commission Regulation on the polyphenols content of olive oils and their beneficial effects on human health.

Impact of yeast starter formulations on the production of volatile compounds during wine fermentation.

The most diffused starter formulation in winemaking is actually represented by active dry yeast (ADY). Spray-drying has been reported as an appropriate preservation method for yeast and other micro-organisms. Despite the numerous advantages of this method, the high air temperatures used can negatively affect cell viability and the fermentative performance of dried cells. In the present study, 11 wine S. cerevisiae strains (both indigenous and commercial) were submitted to spray-drying; different process conditions were tested in order to select the conditions allowing the highest strain survival. The strains exhibited high variability for tolerance to spray-drying treatment. Selected strains were tested in fermentation at laboratory scale in different formulations (free fresh cells, free dried cells, immobilized fresh cells and immobilized dried cells), in order to assess the influence of starter formulation on fermentative fitness of strains and aromatic quality of wine. The analysis of volatile fraction in the experimental wines produced by selected strains in different formulations allowed identification of > 50 aromatic compounds (alcohols, esters, ketones, aldehydes and terpenes). The results obtained showed that the starter formulation significantly influenced the content of volatile compounds. In particular, the wines obtained by strains in dried forms (as both free and immobilized cells) contained higher numbers of volatile compounds than wines obtained from fresh cells.

Wet-dry-wet drug screen leads to the synthesis of TS1, a novel compound reversing lung fibrosis through inhibition of myofibroblast differentiation.

Therapies halting the progression of fibrosis are ineffective and limited. Activated myofibroblasts are emerging as important targets in the progression of fibrotic diseases. Previously, we performed a high-throughput screen on lung fibroblasts and subsequently demonstrated that the inhibition of myofibroblast activation is able to prevent lung fibrosis in bleomycin-treated mice. High-throughput screens are an ideal method of repurposing drugs, yet they contain an intrinsic limitation, which is the size of the library itself. Here, we exploited the data from our "wet" screen and used "dry" machine learning analysis to virtually screen millions of compounds, identifying novel anti-fibrotic hits which target myofibroblast differentiation, many of which were structurally related to dopamine. We synthesized and validated several compounds ex vivo ("wet") and confirmed that both dopamine and its derivative TS1 are powerful inhibitors of myofibroblast activation. We further used RNAi-mediated knock-down and demonstrated that both molecules act through the dopamine receptor 3 and exert their anti-fibrotic effect by inhibiting the canonical transforming growth factor ß pathway. Furthermore, molecular modelling confirmed the capability of TS1 to bind both human and mouse dopamine receptor 3. The anti-fibrotic effect on human cells was confirmed using primary fibroblasts from idiopathic pulmonary fibrosis patients. Finally, TS1 prevented and reversed disease progression in a murine model of lung fibrosis. Both our interdisciplinary approach and our novel compound TS1 are promising tools for understanding and combating lung fibrosis.

Signal-On Fluorescent Imprinted Nanoparticles for Sensing of Phenols in Aqueous Olive Leaves Extracts.

The activation of signals in fluorescent nanosensors upon interaction with their targets is highly desirable. To this aim, several molecularly imprinted nanogels have been synthetized for the recognition of tyrosol, hydroxytyrosol and oleuropein in aqueous extracts using the non-covalent approach. Two of them contain fluorescein derivatives as co-monomers, and their fluorescence emission is switched on upon binding of the target phenols. The selection of functional monomers was previously done by analyzing the interactions by nuclear magnetic resonance (NMR) in deuterated dimethylsulfoxide (DMSO-d6) of the monomers with tyrosol and hydroxytyrosol. Polymers were synthetized under high dilution conditions to obtain micro- and nano-particles, as verified by transmission electron microscopy (TEM). 1,4-Divinylbenzene (DVB) was used in the fluorescent polymers in order to enhance the interactions with the aromatic ring of the templates tyrosol and hydroxytyrosol by π-π stacking. The results were fully satisfactory as to rebinding: DVB-crosslinked molecularly imprinted polymers (MIPs) gave over 50 nmol/mg rebinding. The sensitivity of the fluorescent MIPs was excellent, with LODs in the pM range. The sensing polymers were tested on real olive leaves extracts, with very good performance and negligible matrix effects.

Synthesis, Cytotoxicity Evaluation, and Computational Insights of Novel 1,4-Diazepane-Based Sigma Ligands.

Among several potential applications, sigma receptor ligands can be used as antipsychotics, antiamnesics, and against other neurodegenerative disorders as well as neuroprotective agents. We present herein a new series of diazepane-containing derivatives as σR ligands obtained by a conformational expansion approach of our previously synthesized piperidine-based compounds. The best results were reached by benzofurane 2c, 3c and quinoline 2d, 3d-substituted diazepane derivatives, which showed the highest σR affinity. The cytotoxic activities of synthesized compounds were evaluated against two cancer cell lines, and the results indicated that none of the compounds induced significant toxicity in these cells. We also evaluated the antioxidant activity by radical scavenging capacity of our best compounds on ABTS and H2O2. The results obtained reveal that our new derivatives possess an excellent antioxidant profile and could be protective for the cells. Overall, the benzofurane derivative 2c due to its strong interaction with the active site of the receptor, as confirmed by molecular dynamic simulations, emerged as the optimum compound with high σ1R affinity, low cytotoxicity, and a potent antioxidant activity.

Characterization of white wines from north-eastern Italy with surface-enhanced Raman spectroscopy.

In the present study, label-free SERS spectroscopy is applied as a useful analytical technique for white wine characterization. 180 samples of three white wines varieties from northeastern Italy, Sauvignon Blanc, Ribolla Gialla and Friulano, collected from three different Italian producers from 2016 vintage, have been analyzed using Ag citrate-reduced colloids and a portable Raman instrument with a 785 nm laser. A PCA of SERS spectra showed that discrimination between wines and wineries is possible. Main spectral differences are due to adenine, carboxylic acids and glutathione, with their ratio changing among different wine types and producers. A robust version of the Soft Independent Modelling of Class Analogy (SIMCA) method was used to model the class space of each wine and to perform the classification among the different categories, yielding overall efficiencies between 87 and 93%. These results are extremely encouraging and open the way to the application of this SERS protocol as a wine identification assay.

Discovery of new potent dual sigma receptor/GluN2b ligands with antioxidant property as neuroprotective agents.

Among several potential applications, sigma receptors (σRs) can be used as neuroprotective agents, antiamnesic, antipsychotics and against other neurodegenerative disorders. On the other hands, antagonists of the GluN2b-subunit-containing-N-methyl-D-aspartate (NMDA) receptors are of major interest for the same purpose, being this subunit expressed in specific areas of the central nervous system and responsible for the excitatory regulation of nerve cells. Under these premises, we have synthesized and biologically tested novel hybrid derivatives obtained from the combination of phenyloxadiazolone and dihydroquinolinone scaffolds with different amine moieties, peculiar of σ2R ligands. Most of the new ligands exhibited a pan-affinity towards both σR subtypes and high affinity against GluN2b subunit. The most promising compounds belong to the dihydroquinolinone series, with the best affinity profile for the cyclohexylpiperazine derivative 28. Investigation on their biological activity showed that the new compounds were able to protect SH-SY5Y cells against oxidative stress induced by hydrogen peroxide treatment. These results proved that our dual σR/GluN2b ligands have beneficial effects in a model of neuronal oxidative stress and can represent strong candidate pharmacotherapeutic agents for minimizing oxidative stress-induced neuronal injuries.