Thromboembolic events in beta thalassemia major: an Italian multicenter study

Oxidation of cholesterol (1a) or pregnenolone (1b) with pyridinium dichromate (PDC) in dimethylformamide (DMF) or in dichloromethane (DCM) and pyridinium chlorochromate (PCC) in DCM provided cholest-4-en-3,6-dione (2a) or pregn-4-en-3,6,20-trione (2b). TLC monitoration of the reactions implied that cholest-5-en-3-one (3a) or pregn-5-en-3,20-dione (3b) and cholest-4-en-3-one (4a) or pregn-4-en-3,20-dione (4b) might be intermediates. Individual oxidation of 3a or 3b with PDC and PCC could give 2a or 2b, but 4a or 4b remained unchanged. Further investigation indicated that 4a or 4b was an isomerization product of 3a or 3b on silica gel TLC plate rather than really existence in the reaction mixture. These results shown steroidal 5-en-3-ones were intermediates of the transformation of steroidal 5-en-3 beta-ols to steroidal 4-en-3,6-diones oxidized by PDC and PCC.     

Effects of lipoxygenase and of chemical oxidising agent potassium iodate on rheological properties of durum dough

To study the involvement of lipoxygenase (LOX) and oxidising agent potassium iodate (KIO₃) in rheological behaviour of dough, mixograph and alveograph tests were performed using durum cultivars differing for quality and endogenous levels of LOX. Both tests were done in standard condition and with the adding of KIO₃ and of LOX and/or its substrate, utilised singly or in different combinations. The effects of these treatments were related to change of ‐SH and S–S content in relative mixograph dough. The mixograph and alveograph responses showed that the KIO₃ had an improving effect on dough tenacity and that the adding of LOX system enhanced this trend; on the contrary, the LOX system alone seemed not affect mixing stability. No relation was found between rheological responses and ‐SH and S–S content in the mixograph doughs. The results obtained could suggest that in durum wheat the main effect of LOX could be ascribable to bleaching action because of the co‐oxidation of carotenoid pigments.     

Effect of aldose reductase inhibition on glutathione redox status in erythrocytes of diabetic patients

Diabetic patients undergo a chronic oxidative stress. This phenomenon is demonstrated by low levels of reduced glutathione (GSH) levels. The NADPH used by glutathione reductase for the reduction of oxidized glutathione (GSSG) to GSH is also used by aldose reductase for the reduction of glucose to sorbitol through the polyol pathway. The competition for NADPH could be responsible for the decreased glutathione levels found in non-insulin-dependent diabetic patients. For this purpose, we investigated the effect of polyol pathway inhibition on the glutathione redox status in these patients. We measured GSH and GSSG levels in erythrocytes of non-insulin-dependent diabetic patients (n = 15) before and after 1 week of treatment with placebo, followed by 1 week of treatment with an aldose reductase inhibitor (tolrestat 200 mg/dl). We found lower GSH levels (7.7 +/- 1.4 mumol/g hemoglobin [Hb]), higher GSSG levels (0.35 +/- 0.09 mumol/g Hb), and lower GSH/GSSG ratios (23.9 +/- 7.7) in diabetics compared with controls (n = 15; 9.8 +/- 0.8 mumol/g Hb, P < .001; 0.17 +/- 0.02, P < .001; and 58.3 +/- 9.1, P < .001, respectively). We did not demonstrate any statistical difference after 1 week of treatment with placebo. In contrast, the treatment with tolrestat induced a significant increase in GSH (8.9 +/- 0.7 mumol/g Hb, P < .01), a decrease in GSSG (0.25 +/- 0.06 mumol/g Hb, P < .02), and an increase in the GSH/GSSG ratio (37.3 +/- 8.4, P < .01). These data strongly support the hypothesis that the polyol pathway plays an important role in the impairment of the glutathione redox status in diabetic patients.     

The effects of various processing conditions on a protein isolate from Lupinus angustifolius

Lupin protein is a promising ingredient in functional foods because of its purported hypocholesterolaemic and hypotensive activities. In this study a lupin protein isolate from Lupinus angustifolius was thermally and mechanically treated and the effects on its protein profile were determined. As a preliminary step, the main protein components of L. angustifolius were identified, using the canonical proteomic approach, including 2D-separation and mass spectrometry and, whenever necessary, also “de novo peptide sequencing”. Most of the main spots were assigned to the major lupin storage proteins: α-conglutin, β-conglutin, γ-conglutin, and δ-conglutin. The protein degradation induced by the different treatments was studied via differential scanning calorimetry (DSC), 2D-electrophoresis, and mass spectrometry, in order to get the fingerprint of the intact peptides after processing. The results indicate that, even after harsh industrial processing, α-, β- and δ-conglutin are still able to release stable peptides, although they are completely or partially degraded, as shown by the 2D protein profiles and the DSC graphs.     

Effect of ultrasound treatment on properties of gluten-based film

Gluten films obtained in acid conditions display some protein dispersion difficulties. Ultrasound treatment (UT) could represent an interesting strategy for improving gluten film appearance. Different UT exposure times were applied to film-forming dispersion. The aim of this work was to investigate the effect of ultrasound treatment on gluten-based films at molecular and mesoscopic levels. Distribution in gliadin and glutenins was determined with SE-HPLC. The UT improved protein dispersion and final film appearance. Sonication did not lead to large changes in various gluten fractions, which suggests absence of important protein breakdown at the molecular level. Gluten showed high tolerance to UT. Surface properties of untreated and treated films were investigated by contact angle measurement: sonication promoted hydrophilic surface properties.Industrial relevanceBio-based packaging has been receiving increasing attention in view of its beneficial impact on the environment. Among proteins, gluten resulted as a very interesting film-forming material. Gluten films prepared in acid conditions showed problems in protein dispersion. Sonication represents a physical strategy which allowed us to obtain gluten-based films without the addition of chemical additives, such as sodium sulphite.     

Synthesis and association properties of thermoresponsive and permanently cationic charged block copolymers

Atom transfer radical polymerization (ATRP) was used to prepare thermosensitive cationic block copolymers of (3-acrylamidopropyl)-trimethylammonium chloride (AMPTMA) and N-isopropylacrylamide (NIPAAM) with different block lengths. By using ethyl-2-chloropropionate (ECP) as initiator and CuCl/CuCl₂/tris(2-dimethylaminoethyl)amine (Me₆TREN) catalytic system in DMF:water 50:50 (v/v) mixtures at 20 °C the polymerization was controlled. The association properties in NaCl aqueous solution were studied as a function of temperature and polymer concentration by dynamic light scattering, NMR spectroscopy, fluorescence spectroscopy and energy filtered-transmission electron microscopy. The block copolymers formed micellar aggregates above the lower critical solution temperature (LCST) of pNIPAAM. The LCST is strongly influenced by the relative length of the two blocks and is significantly higher than that of pure pNIPAAM. The size of core and shell of the micelles is discussed in terms of block copolymer composition.     

Discovery and Pharmacophore Mapping of a Low-Nanomolar Inhibitor of P. falciparum Growth

The treatment of malaria, the most common parasitic disease worldwide and the third deadliest infection after HIV and tuberculosis, is currently compromised by the dramatic increase and diffusion of drug resistance among the various species of Plasmodium, especially P. falciparum (Pf). In this view, the development of new antiplasmodial agents that are able to act via innovative mechanisms of action, is crucial to ensure efficacious antimalarial treatments. In one of our previous communications, we described a novel class of compounds endowed with high antiplasmodial activity, characterized by a pharmacophore never described before as antiplasmodial and identified by their 4,4’-oxybisbenzoyl amide cores. Here, through a detailed structure-activity relationship (SAR) study, we thoroughly investigated the chemical features of the reported scaffolds and successfully built a novel antiplasmodial agent active on both chloroquine (CQ)-sensitive and CQ-resistant Pf strains in the low nanomolar range, without displaying cross-resistance. Moreover, we conducted an in silico pharmacophore mapping.     

Interactive Multi‐objective Dynamic Optimization of Bioreactors under Parametric Uncertainty

Model‐based optimization techniques play a key role in achieving a sustainable operation of biochemical processes. Models are an approximation of the real process under study, hence, uncertainty is inherently present and for a sustainable process operation this uncertainty should be accounted for. In practice, optimality with respect to different conflicting objectives is required and multi‐objective optimization is a valuable tool. In this article the sigma point approach is applied to account for parametric uncertainty in the frame of interactive multi‐objective bioprocess optimization.     

Chemical characterisation of Thymus populations belonging from Southern Italy

The genus Thymus L. consists of many species of herbaceous perennials and sub-shrubs. A chemical characterisation of a collection of Thymus spp. originated from regions of Southern Italy was performed using GC and GC/MS. The accessions were collected from various natural habitats of the Basilicata and Puglia Regions and transferred into a new uniform environment. The study showed that amongst the 22 components of the oils the most recurrent ones were geraniol, thymol and α-terpinene followed by linalool, citral and trans-caryophillene. Cluster analysis led to the identification of two chemotypes: geraniol and thymol/α-terpinene; only a biotype remained separate from all others, probably because of its high content linalool (58%).     

Inhibition of the FGF/FGFR System Induces Apoptosis in Lung Cancer Cells via c-Myc Downregulation and Oxidative Stress

Lung cancer represents an extremely diffused neoplastic disorder with different histological/molecular features. Among the different lung tumors, non-small-cell lung cancer (NSCLC) is the most represented histotype, characterized by various molecular markers, including the expression/overexpression of the fibroblast growth factor receptor-1 (FGFR1). Thus, FGF/FGFR blockade by tyrosine kinase inhibitors (TKi) or FGF-ligand inhibitors may represent a promising therapeutic approach in lung cancers. In this study we demonstrate the potential therapeutic benefit of targeting the FGF/FGFR system in FGF-dependent lung tumor cells using FGF trapping (NSC12) or TKi (erdafitinib) approaches. The results show that inhibition of FGF/FGFR by NSC12 or erdafitinib induces apoptosis in FGF-dependent human squamous cell carcinoma NCI-H1581 and NCI-H520 cells. Induction of oxidative stress is the main mechanism responsible for the therapeutic/pro-apoptotic effect exerted by both NSC12 and erdafitinib, with apoptosis being abolished by antioxidant treatments. Finally, reduction of c-Myc protein levels appears to strictly determine the onset of oxidative stress and the therapeutic response to FGF/FGFR inhibition, indicating c-Myc as a key downstream effector of FGF/FGFR signaling in FGF-dependent lung cancers.