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Saprolegnia spp. water molds severely impact fish health in aquaculture, fish farms and hobby fish tanks colonizing mature and immature stages of fishes, as well as eggs. Considering that there are no drugs licensed for treating and/or control the organism, efficient and environmental low-impact methods to control these oomycetes in aquaculture are needed. The aim of the present report was to evaluate the in vitro sensitivity of Saprolegnia parasitica to essential oils (EOs) from Citrus aurantium L., Citrus bergamia Risso et Poiteau, Citrus limon Burm. f., Citrus paradisi Macfad, Citrus sinensis Osbeck, Cinnamomum zeylanicum Blume, Cymbopogon flexuosum (Nees ex Steud.) Watson, Foeniculum vulgare Mill., Illicium verum Hook.f., Litsea cubeba (Lour.) Pers., Origanum majorana L., Origanum vulgare L., Pelargonium graveolens L&rsquo, H&eacute, r., Syzygium aromaticum Merr. &amp, L.M.Perry, and Thymus vulgaris L., by microdilution test. The most effective EOs assayed were T. vulgaris and O. vulgare, followed by C. flexuosum, L. cubeba and C. bergamia. These EOs could be of interest for controlling Saprolegnia infections. Nevertheless, further safety studies are necessary to evaluate if these products could be dispersed in tank waters, or if their use should be limited to aquaculture supplies.

Background: Galium is a plant rich in iridoid glycosides, flavonoids, anthraquinones, and small amounts of essential oils and vitamin C. Recent works showed the antibacterial, antifungal, antiparasitic, and antioxidant activity of this plant genus. Methods: For the determination of the multicomponent phenolic pattern, liquid phase microextraction procedures were applied, combined with HPLC-PDA instrument configuration in five Galium species aerial parts (G. verum, G. album, G. rivale, G. pseudoaristatum, and G. purpureum). Dispersive Liquid&ndash, Liquid MicroExtraction (DLLME) with NaCl and NAtural Deep Eutectic Solvent (NADES) medium and Ultrasound-Assisted (UA)-DLLME with &beta, cyclodextrin medium were optimized. Results: The optimal DLLME conditions were found to be: 10 mg of the sample, 10% NaCl, 15% NADES or 1% &beta, cyclodextrin as extraction solvent&mdash, 400 &mu, L of ethyl acetate as dispersive solvent&mdash, 300 &mu, L of ethanol, vortex time&mdash, 30 s, extraction time&mdash, 1 min, centrifugation at 12000&times, g for 5 min. Conclusions: These results were compared with microwave-assisted extraction procedures. G. purpureum and G. verum extracts showed the highest total phenolic and flavonoid content, respectively. The most potent extract in terms of antioxidant capacity was obtained from G. purpureum, whereas the extract obtained from G. album exhibited the strongest inhibitory effect against tyrosinase.

Processing and shaping of dried gels are of interest in several fields like alginate aerogel beads used as highly porous and nanostructured particles in biomedical applications. The physicochemical properties of the alginate source, the solvent used in the gelation solution and the gel drying method are key parameters influencing the characteristics of the resulting dried gels. In this work, dried gel beads in the form of xerogels, cryogels or aerogels were prepared from alginates of different molecular weights (120 and 180 kDa) and concentrations (1.25, 1.50, 2.0 and 2.25% (w/v)) using different gelation conditions (aqueous and ethanolic CaCl2 solutions) and drying methods (supercritical drying, freeze-drying and oven drying) to obtain particles with a broad range of physicochemical and textural properties. The stability of physicochemical properties of alginate aerogels under storage conditions of 25 &deg, C and 65% relative humidity (ICH-climatic zone II) during 1 and 3 months was studied. Results showed significant effects of the studied processing parameters on the resulting alginate dried gel properties. Stability studies showed small variations in aerogels weight and specific surface area after 3 months of storage, especially, in the case of aerogels produced with medium molecular weight alginate.

Carbapenem-resistant Acinetobacter baumannii (CR-Ab) infections are associated with high morbidity and mortality. The aim of the study was to evaluate the in-vitro activity of different antimicrobial combinations (with and without colistin, COL) against clinical isolates of CR-Ab collected from patients with CR-Ab infection, including unconventional combinations such as COL + VANcomycin (VAN) and COL + rifampin (RIF). CR-Ab strains were collected from hospitalized patients at Sapienza University of Rome. Antimicrobial susceptibility patterns were determined throughout MIC50/90s whereas the synergistic activity was evaluated by qualitative (i.e., checkerboard) and quantitative (i.e., killing studies) methods. All the strains were found oxacillinase (OXA) producers and tigecycline (TIG) sensitive whereas 2 strains were resistant to COL. Application of the checkerboard method indicated complete synergism in COL combinations at different extension: 21.4%, 57.1%, 42.8%, 35.7% for COL + meropenem (MEM), COL + RIF, COL + VAN and COL + TIG, respectively, with the non-conventional combinations COL + VAN and COL + RIF exhibiting the highest rate of synergism. Regarding COL-free combination, complete synergism was observed in 35.7% of the strains for MEM + TIG. Killing studies showed that the combinations COL + MEM, COL + TIG and MEM + TIG were bactericidal and synergistic against both colistin-sensitive and low colistin-resistant strains whereas only the combinations COL + VAN and COL + RIF showed an early and durable bactericidal activity against all the tested strains, with absence of growth at 24 h. This study demonstrated that COL-based combinations lead to a high level of synergic and bactericidal activity, especially COL + VAN and COL + RIF, even in the presence of high level of COL resistance.

Triterpene acid and phenolic constituents from nine ancient varieties of apple (Malus domestica) fruits cultivated in Fanna, Friuli Venezia Giulia region, northeast Italy, were analyzed and compared with four commercial apples (&lsquo, Golden Delicious&rsquo, &lsquo, Red Delicious&rsquo, Granny Smith&rsquo, and &lsquo, Royal Gala&rsquo, ). Total phenolic and flavonoid contents were measured by spectrophotometric assays. The quali-quantitative fingerprint of secondary metabolites including triterpene acid was obtained by LC-DAD-(ESI)-MS and LC-(APCI)-MS, respectively. Based on the two LC-MS datasets, multivariate analysis was used to compare the composition of ancient fruit varieties with those of four commercial apples. Significant differences related mainly to the pattern of triterpene acids were found. Pomolic, euscaphyc, maslinic and ursolic acids are the most abundant triterpene in ancient varieties pulps and peels, while ursolic and oleanolic acids were prevalent in the commercial fruits. Also, the content of the phenolic compounds phloretin-2-O-xyloglucoside and quercetin-3-O-arabinoside was greater in ancient apple varieties. The antioxidant (radical scavenging, reducing power, metal chelating and phosphomolybdenum assays) and enzyme inhibitory effects (against cholinesterase, tyrosinase, amylase and glucosidase) of the samples were investigated in vitro. Antioxidant assays showed that the peels were more active than pulps. However, all the samples exhibited similar enzyme inhibitory effects. Ancient Friuli Venezia Giulia apple cultivars can be a source of chlorogenic acid and various triterpene acids, which are known for their potential anti-inflammatory activity and beneficial effects on lipid and glucose metabolism. Our results make these ancient varieties suitable for the development of new nutraceutical ingredients.

Every year Chile exports about 2000 tons of boldo folium (Peumus boldus), which is used around the world as a traditional herbal medicinal product (THMP), mostly to relieve gastrointestinal disorders. This biomass may be a resource for the agrochemical industry to manufacture botanical insecticides. In this regard, the insecticidal potential of boldo has been poorly investigated. In the present work, hydrodistillation of a commercial boldo folium gave 1.5% (w/w) of a yellowish essential oil (boldo essential oil, BEO) containing 1,8-cineole (20.7%), p-cymene (18.5%), limonene (9.1%), ascaridole (9.1%) and &beta, phellandrene (6.4%) as the main constituents, as determined by gas chromatography-mass spectrometry (GC-MS). NMR analysis allowed us to determine that ascaridole was mainly represented by the cis-isomer. BEO was toxic to larvae of the filariasis vector Culex quinquefasciatus and adults of the housefly Musca domestica, showing LC50/LD50 values of 67.9 mg&middot, L&minus, 1 and 98.5 &micro, g&middot, adult&minus, 1, respectively. On the other hand, lower insecticidal activity was observed against larvae of the moth pest Spodoptera littoralis (LD50 of 268.9 &micro, larva&minus, 1). It is worth noting that, when tested at LC90 concentration, BEO was significantly less toxic to aquatic microcrustacean Daphnia magna than the conventional insecticide &alpha, cypermethrin. Finally, in the attempt to explore the BEO mode of action, we tested it for acetylcholinesterase (AChE) inhibitory properties using the Ellman method, obtaining negligible effects (IC50 = 0.45 mg&middot, mL&minus, 1). Taken together, these results gave new insights into the potential of BEO as a future ingredient of botanical insecticides.

Trifluoromethylselenolated carbonyl compounds represent an emerging class with potential applications in several fields, however, a widespread use of such compound is hampered by the very limited number of strategies for their preparation. In this study we developed a method for the preparation of &alpha, SeCF3 substituted carbonyl derivatives using an in situ generated electrophilic ClSeCF3 species. We also implemented an in-flow protocol to improve the safety features of the process.

A multi-layer artificial neural network (ANN) was used to model the retention behavior of 16 o-phthalaldehyde derivatives of amino acids in reversed-phase liquid chromatography under application of various gradient elution modes. The retention data, taken from literature, were collected in acetonitrile&ndash, water eluents under application of linear organic modifier gradients ( gradients), pH gradients, or double pH/ gradients. At first, retention data collected in  gradients and pH gradients were modeled separately, while these were successively combined in one dataset and fitted simultaneously. Specific ANN-based models were generated by combining the descriptors of the gradient profiles with 16 inputs representing the amino acids and providing the retention time of these solutes as the response. Categorical &ldquo, bit-string&rdquo, descriptors were adopted to identify the solutes, which allowed simultaneously modeling the retention times of all 16 target amino acids. The ANN-based models tested on external gradients provided mean errors for the predicted retention times of 1.1% ( gradients), 1.4% (pH gradients), 2.5% (combined  and pH gradients), and 2.5% (double pH/ gradients). The accuracy of ANN prediction was better than that previously obtained by fitting of the same data with retention models based on the solution of the fundamental equation of gradient elution.

The aqueous extract of dry onion skin waste from the &lsquo, Dorata di Parma&rsquo, cultivar was tested as a new source of biomolecules for the production of colored and biofunctional wool yarns, through environmentally friendly dyeing procedures. Specific attention was paid to the antioxidant and UV protection properties of the resulting textiles. On the basis of spectrophotometric and mass spectrometry analyses, the obtained deep red-brown color was assigned to quercetin and its glycoside derivatives. The Folin&ndash, Ciocalteu method revealed good phenol uptakes on the wool fiber (higher than 27% for the textile after the first dyeing cycle), with respect to the original total content estimated in the water extract (78.50 &plusmn, 2.49 mg equivalent gallic acid/g onion skin). The manufactured materials showed remarkable antioxidant activity and ability to protect human skin against lipid peroxidation following UV radiation: 7.65 &plusmn, 1.43 (FRAP assay) and 13.60 (ORAC assay) mg equivalent trolox/g textile, lipid peroxidation inhibition up to 89.37%. This photoprotective and antioxidant activity were therefore ascribed to the polyphenol pool contained in the outer dried gold skins of onion. It is worth noting that citofluorimetric analysis demonstrated that the aqueous extract does not have a significative influence on cell viability, neither is capable of inducing a proapoptotic effect.

A lack of specificity is restricting the further application of conotoxin from Conus bullatus (BuIA). In this study, an analogue library of BuIA was established and virtual screening was used, which identified high &alpha, 7 nicotinic acetylcholine receptor (nAChR)-selectivity analogues. The analogues were synthesized and tested for their affinity to functional human &alpha, 7 nAChR and for the regulation of intracellular calcium ion capacity in neurons. Immunofluorescence, flow cytometry, and patch clamp results showed that the analogues maintained their capacity for calcium regulation. The results of the hot-plate model and paclitaxel-induced peripheral neuropathy model indicated that, when compared with natural BuIA, the analgesia activities of the analogues in different models were maintained. To analyze the adverse effects and toxicity of BuIA and its analogues, the tail suspension test, forced swimming test, and open field test were used. The results showed that the safety and toxicity of the analogues were significantly better than BuIA. The analogues of BuIA with an appropriate and rational mutation showed high selectivity and maintained the regulation of Ca2+ capacity in neurons and activities of analgesia, whereas the analogues demonstrated that the adverse effects of natural &alpha, conotoxins could be reduced.

St. John’s Wort (Hypericum perforatum L.) flowers are commonly used in ethnomedical preparations with promising outcomes to treat inflammation both per os and by topical application. However, the underlying molecular mechanisms need to be described toward a rational, evidence-based, and reproducible use. For this purpose, the aptitude of the prominent Hypericum metabolite hypericin was assessed, along with that of its main congeners, to behave as an inhibitor of janus kinase 1, a relevant enzyme in inflammatory response. It was used a molecular modeling approach relying on docking simulations, pharmacophoric modeling, and molecular dynamics to estimate the capability of molecules to interact and persist within the enzyme pocket. Our results highlighted the capability of hypericin, and some of its analogues and metabolites, to behave as ATP-competitive inhibitor providing: (i) a likely mechanistic elucidation of anti-inflammatory activity of H. perforatum extracts containing hypericin and related compounds, and (ii) a rational-based prioritization of H. perforatum components to further characterize their actual effectiveness as anti-inflammatory agents.

Phoma-like fungi are known as producers of diverse spectrum of secondary metabolites, including phytotoxins. Our bioassays had shown that extracts of Paraphoma sp. VIZR 1.46, a pathogen of Cirsium arvense, are phytotoxic. In this study, two phytotoxically active metabolites were isolated from Paraphoma sp. VIZR 1.46 liquid and solid cultures and identified as curvulin and phaeosphaeride A, respectively. The latter is reported also for the first time as a fungal phytotoxic product with potential herbicidal activity. Both metabolites were assayed for phytotoxic, antimicrobial and zootoxic activities. Curvulin and phaeosphaeride A were tested on weedy and agrarian plants, fungi, Gram-positive and Gram-negative bacteria, and on paramecia. Curvulin was shown to be weakly phytotoxic, while phaeosphaeride A caused severe necrotic lesions on all the tested plants. To evaluate phaeosphaeride A&rsquo, s herbicidal efficacy, the phytotoxic activity of this compound in combination with five different adjuvants was studied. Hasten at 0.1% (v/v) was found to be the most potent and compatible adjuvant, and its combination with 0.5% (v/v) semi-purified extract of Paraphoma sp. VIZR 1.46 solid culture exhibited maximum damage to C. arvense plants. These findings may offer significant importance for further investigation of herbicidal potential of phaeosphaeride A and possibly in devising new herbicide of natural origin.

The immune system is an efficient integrated network of cellular elements and chemicals developed to preserve the integrity of the organism against external insults and its correct functioning and balance are essential to avoid the occurrence of a great variety of disorders. To date, evidence from literature highlights an increase in immunological diseases and a great attention has been focused on the development of molecules able to modulate the immune response. There is an enormous global demand for new effective therapies and researchers are investigating new fields. One promising strategy is the use of herbal medicines as integrative, complementary and preventive therapy. The active components in medical plants have always been an important source of clinical therapeutics and the study of their molecular pharmacology is an enormous challenge since they offer a great chemical diversity with often multi-pharmacological activity. In this review, we mainly analysed the immunomodulatory/antinflammatory activity of Echinacea spp. and Curcuma longa, focusing on some issues of the phytochemical research and on new possible strategies to obtain novel agents to supplement the present therapies.

Chlorogenic acid (CGA) is a very common dietary polyphenolic compound. CGA is becoming very attractive due to its potential use as preventive and therapeutic agent in many diseases, including cancer. Inorganic/organic hybrid materials are gaining considerable attention in the biomedical field. The sol-gel process provides a useful way to obtain functional organic/inorganic hybrids. The aim of this study was to synthesize silica/polyethylene glycol (PEG) hybrids with different percentages of CGA by sol-gel technique and to investigate their impact on the cancer cell proliferation. Synthesized materials have been chemically characterized through the FTIR spectroscopy and their bioactivity evaluated looking by SEM at their ability to produce a hydroxyapatite layer on their surface upon incubation with simulated body fluid (SBF). Finally, their effects on cell proliferation were studied in cell lines by direct cell number counting, MTT, flow cytometry-based cell-cycle and cell death assays, and immunoblotting experiments. Notably, we found that SiO2/PEG/CGA hybrids exhibit clear antiproliferative effects in different tumor, including breast cancer and osteosarcoma, cell lines in a CGA dependent manner, but not in normal cells. Overall, our results increase the evidence of CGA as a possible anticancer agent and illustrate the potential for clinical applications of sol-gel synthesized SiO2/PEG/CGA materials.

Alzheimer’s disease still represents an untreated multifaceted pathology, and drugs able to stop or reverse its progression are urgently needed. In this paper, a series of naturally inspired chalcone-based derivatives were designed as structural simplification of our previously reported benzofuran lead compound, aiming at targeting both acetyl (AChE)- and butyryl (BuChE) cholinesterases that, despite having been studied for years, still deserve considerable attention. In addition, the new compounds could also modulate different pathways involved in disease progression, due to the peculiar trans-α,β-unsaturated ketone in the chalcone framework. All molecules presented in this study were evaluated for cholinesterase inhibition on the human enzymes and for antioxidant and neuroprotective activities on a SH-SY5Y cell line. The results proved that almost all the new compounds were low micromolar inhibitors, showing different selectivity depending on the appended substituent, some of them were also effective antioxidant and neuroprotective agents. In particular, compound 4, endowed with dual AChE/BuChE inhibitory activity, was able to decrease ROS formation and increase GSH levels, resulting in enhanced antioxidant endogenous defense. Moreover, this compound also proved to counteract the neurotoxicity elicited by Aβ1–42 oligomers, showing a promising neuroprotective potential.

The development of new strategies for enhancing drug delivery to the brain represents a major challenge in treating cerebral diseases. In this paper, we report on the synthesis and structural characterization of a biocompatible nanoparticle (NP) made up of poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) co-polymer (namely PELGA) functionalized with the membranotropic peptide gH625 (gH) and the iron-mimicking peptide CRTIGPSVC (CRT) for transport across the blood-brain barrier (BBB). gH possesses a high translocation potency of the cell membrane. Conversely, CRT selectively recognizes the brain endothelium, which interacts with transferrin (Tf) and its receptor (TfR) through a non-canonical ligand-directed mechanism. We hypothesize that the delivery across the BBB of PELGA NPs should be efficiently enhanced by the NP functionalization with both gH and CRT. Synthesis of peptides and their conjugation to the PLGA as well as NP physical-chemical characterization are performed. Moreover, NP uptake, co-localization, adhesion under dynamic conditions, and permeation across in vitro BBB model are evaluated as a function of gH/CRT functionalization ratio. Results establish that the cooperative effect of CRT and gH may change the intra-cellular distribution of NPs and strengthen NP delivery across the BBB at the functionalization ratio 33% gH&ndash, 66% CRT.

(+)-epi-Epoformin (1), is a fungal cyclohexene epoxide isolated together with diplopimarane and sphaeropsidins A and C, a nor-ent-pimarane and two pimaranes, from the culture filtrates of Diplodia quercivora, a fungal pathogen for cork oak in Sardinia, Italy. Compound 1 possesses a plethora of biological activities including: antifungal, zootoxic and phytotoxic activity. The last activity and the peculiar structural feature of 1 suggested to carry out a structure activity relationship study, preparing eight key hemisynthetic derivatives and their phytotoxicity was assayed. The complete spectroscopic characterization and the activity in the etiolated wheat coleoptile bioassay of all the compounds is reported. Most of the compounds inhibited growth and some of them had comparable or higher activity than the natural product and the reference herbicide Logran. As regards the structure-activity relationship, the carbonyl proved to be essential for their activity of 1, as well as the conjugated double bond, while the epoxide could be altered with no significant loss.

Cannabis sativa active compounds are extensively studied for their therapeutic effects, beyond the well-known psychotropic activity. C. Sativa is used to treat different medical indications, such as multiple sclerosis, spasticity, epilepsy, ulcerative colitis and pain. Simultaneously, basic research is discovering new constituents of cannabis-derived compounds and their receptors capable of neuroprotection and neuronal activity modulation. The function of the various phytochemicals in different therapeutic processes is not fully understood, but their significant role is starting to emerge and be appreciated. In this review, we will consider the structure-activity relationship (SAR) of cannabinoid compounds able to bind to cannabinoid receptors and act as therapeutic agents in neuronal diseases, e.g., Parkinson’s disease.

The current study aimed to provide a comprehensive bibliometric overview of the literature on curcumin, complementing the previous reviews and meta-analyses on its potential health benefits. Bibliometric data for the current analysis were extracted from the Web of Science Core Collection database, using the search string TOPIC=(&ldquo, curcumin*&rdquo, ), and analyzed by the VOSviewer software. The search yielded 18,036 manuscripts. The ratio of original articles to reviews was 10.4:1. More than half of the papers have been published since 2014. The major contributing countries were the United States, China, India, Japan, and South Korea. These publications were mainly published in journals representing the following scientific disciplines: biochemistry, chemistry, oncology, and pharmacology. There was a significant positive correlation between the total publication count and averaged citations per manuscript for affiliations, but not for countries/regions and journals. Chemicals that were frequently mentioned in the keywords of evaluated curcumin publications included curcuminoids, resveratrol, chitosan, flavonoids, quercetin, and polyphenols. The literature mainly focused on curcumin&rsquo, s effects against cancer, inflammation, and oxidative stress. Cancer types most frequently investigated were breast, colon, colorectal, pancreatic, and prostate cancers.

Lutein has several benefits for human health, playing an important role in the prevention of age-related macular degeneration (AMD), cataracts, amelioration of the first stages of atherosclerosis, and some types of cancer. In this work, the Scenedesmus almeriensis microalga was used as a natural source for the supercritical fluid (SF) extraction of lutein. For this purpose, the optimization of the main parameters affecting the extraction, such as biomass pre-treatment, temperature, pressure, and carbon dioxide (CO2) flow rate, was performed. In the first stage, the effect of mechanical pre-treatment (diatomaceous earth (DE) and biomass mixing in the range 0.25&ndash, 1 DE/biomass, grinding speed varying between 0 and 600 rpm, and pre-treatment time changing from 2.5 to 10 min), was evaluated on lutein extraction efficiency. In the second stage, the influence of SF-CO2 extraction parameters such as pressure (25&ndash, 55 MPa), temperature (50 and 65 &deg, C), and CO2 flow rate (7.24 and 14.48 g/min) on lutein recovery and purity was investigated. The results demonstrated that by increasing temperature, pressure, and CO2 flow rate lutein recovery and purity were improved. The maximum lutein recovery (~98%) with purity of ~34% was achieved operating at 65 &deg, C and 55 MPa with a CO2 flow rate of 14.48 g/min. Therefore, optimum conditions could be useful in food industries for lutein supplementation in food products.

The growing interest towards essential oils stems from their biological capabilities that include antibacterial and antioxidant effects. Such properties may be extremely useful in the reproductive field, nonetheless essential oils show toxic effects that can lead to cell disruption. The present study aimed to evaluate and compare the effects of tea tree oil (TTO) and its principal component terpinen-4-ol (TER) on the morpho-functional parameters of swine spermatozoa. Experimental samples were prepared by suspending 15 &times, 107 spermatozoa in 5 mL of medium with different concentrations of the above-mentioned compounds: from 0.2 to 2 mg/mL at an interval of 0.2 for TTO, while TER concentrations were adjusted according to its presence in TTO (41.5%). After 3 h incubation at 16 &deg, C, samples were analyzed for pH, viability, acrosome status, and objective motility. The results highlighted a concentration-dependent effect of TTO with total motility as the most sensitive parameter. TER was better tolerated, and the most sensitive parameters were related to membrane integrity, suggesting a different pattern of interaction. The study confirms the importance of evaluating the effects of natural compounds on spermatozoa before exploiting their beneficial effects. Spermatozoa seem to be good candidates for preliminary toxicological screenings in the light of their peculiar properties.

Microalgae Dunaliella salina contains useful molecules such as &beta, carotene and fatty acids (FAs), which are considered high value-added compounds. To extract these molecules, supercritical carbon dioxide was used at different operative conditions. The effects of mechanical pre-treatment (grinding speed at 0&ndash, 600 rpm, pre-treatment time of 2.5&ndash, 7.5 min) and operating parameters for extraction, such as biomass loading (2.45 and 7.53 g), pressure (100&ndash, 550 bars), temperature (50&ndash, 75 &deg, C) and CO2 flow rate (7.24 and 14.48 g/min) by varying the extraction times (30&ndash, 110 min) were evaluated. Results showed that the maximum cumulative recovery (25.48%) of &beta, carotene was achieved at 400 bars and 65 &deg, C with a CO2 flow rate of 14.48 g/min, while the highest purity for stage (55.40%) was attained at 550 bars and 65 &deg, C with a CO2 flow rate of 14.48 g/min. The maximum recovery of FAs, equal to 8.47 mg/g, was achieved at 550 bars and 75 &deg, C with a CO2 flow rate of 14.48 g/min. Moreover, the lowest biomass loading (2.45 g) and the first extraction cycle (30 min) allowed the maximum extraction of &beta, carotene and FAs.

Gelatin is a biopolymer with interesting properties that can be useful for biomaterial design for different applications such as drug delivery systems, or 3D scaffolds for tissue engineering. However, gelatin suffers from poor mechanical stability at physiological temperature, hence methods for improving its properties are highly desirable. In the present work, a new chemical cross-linking strategy based on triazolinedione ene-type chemistry towards stable hydrogel is proposed. Two different homobifunctional 1,2,4-triazoline-3,5(4H)-diones, namely 4,4&prime, hexane-1,6-diylbis(3H-1,2,4-triazoline-3,5(4H)-dione) 1 and 4,4&prime, [methylenebis(4,1-phenylene)]bis(3H-1,2,4-triazoline-3,5(4H)-dione) 2 were used as cross-linkers in different ratio to tyrosine residues in gelatin. The reaction was proved effective in all experimented conditions and hydrogels featured with different thermal stability were obtained. In general, the higher the cross-linker/tyrosine ratio, the more thermostable the hydrogel. The swelling properties are strictly dependent upon the chemical nature of the cross-linker.

We report of the interactions between four amino acids lysine (Lys), arginine (Arg), histidine (His), and phenylalanine (Phe) with the J-aggregates of the protonated 5,10,15,20-tetrakis(4-sulfonatophenyl)-porphyrin H4TPPS. Several aspects of these self-assembled systems have been analyzed: (i) the chiral transfer process, (ii) the hierarchical effects leading to the aggregates formation, and, (iii) the influence of the amino acid concentrations on both transferring and storing chiral information. We have demonstrated that the efficient control on the J-aggregates chirality is obtained when all amino acids are tested and that the chirality transfer process is under hierarchical control. Finally, the chiral porphyrin aggregates obtained exhibit strong chiral inertia.

As a follow-up to our previous studies on differently substituted 1,4-dihydropyridines endowed with a peculiar cardiac selectivity, in this paper, a small series of hybrid compounds bearing the pharmacophore fragment of lidoflazine in position 2 or 3 on a 4-(xanthen-9-one)-dihydropyridine core was reported. Lidoflazine was selected due to our promising previously reported data, and the xanthen-9-one substituent was introduced in position 4 of the dihydropyridine scaffold based on the cardiac selectivity observed in several of our studies. The new hybrid compounds were tested to assess cardiac and vascular activities, and the data were evaluated in comparison with those previously obtained for 4-(xanthen-9-one)-dihydropyridines and lidoflazine&ndash, nifedipine hybrid compounds. The functional studies indicated an interesting peculiar selectivity for the cardiac parameter inotropy, in particular when the lidoflazine fragment was introduced in position 2 of the dihydropyridine scaffold (4a&ndash, e), and thus a possible preferential binding with the Cav 1.2 isoform of l-type calcium channels, which are mainly involved in cardiac contractility.

Many vegetable extracts, essential oils, and their main constituents are active on the Central Nervous System (CNS). In fact, they have been used as sedatives, hypnotics, or tranquilizers for their activity in treating CNS disorders. In this research, we studied the possible activities of Lavandula angustifolia (LA) essential oil and of its main constituent, linalool, as anti-stress compounds on anxiety and social interaction and their in vitro effects on proteins (pERK and PKA) involved in the transmission of the signal. An acute intraperitoneal injection of linalool (100 mg/kg) and of LA essential oil (200 mg/kg) reduced motor activity without any anxiolytic effect, but significantly increased social interaction. Stressed mice, after being exposed to a social defeat encounter, showed heightened anxiety and social avoidance. Acute administration of LA essential oil blocked stress-induced anxiety, while linalool showed no effects. However, both compounds were capable of reversing social aversion, acting as antidepressant agents. Our results showed that linalool inhibits pERK and PKA expression in the SH-SY5Y cell, but no effect was detected with the LA essential oil. Therefore, the LA essential oil and linalool may be considered as useful alternative tools to the available traditional treatments for social stress-induced mental illnesses.

Purpose: Herein, an extended investigation of Tea tree oil (TTO) against a number of multi-drug resistant (MDR) microorganisms in liquid and vapor phases is reported. Methods: The activity of TTO was tested against methicillin-sensitive Staphylococcus aureus (MSSA), Escherichia coli, and clinical strains of methicillin-resistant S. aureus (MRSA), extended-spectrum beta lactamases producer carbapenem-sensitive Klebsiella pneumoniae (ESBL-CS-Kp), carbapenem-resistant K. pneumoniae (CR-Kp), Acinetobacter baumannii (CR-Ab), and Pseudomonas aeruginosa (CR-Pa). Minimal inhibitory/bactericidal concentrations (MIC/MBCs) and synergistic activity between TTO and different antimicrobials were determined. In the vapor assay (VP), TTO-impregnated discs were placed on the lid of a petri dish and incubated for 24 h at 37 °C. Results: TTO showed a potent bactericidal activity against all the tested microorganisms. TTO in combination with each reference antimicrobial showed a high level of synergism at sub-inhibitory concentrations, particularly with oxacillin (OXA) against MRSA. The VP assay showed high activity of TTO against CR-Ab. Conclusion: Evaluation of in-vitro activity clearly indicated TTO as a potential effective antimicrobial treatment either alone or in association with known drugs against MDR. Therefore, TTO could represent the basis for a possible role in non-conventional regimens against S. aureus and Gram-negative MDR. TTO in VP might represent a promising option for local therapy of pneumonia caused by CR-Ab.

Reversine is a potent antitumor 2,6-diamino-substituted purine acting as an Aurora kinases inhibitor and interfering with cancer cell cycle progression. In this study we describe three reversine-related molecules, designed by docking calculation, that present structural modifications in the diamino units at positions 2 and 6. We investigated the conformations of the most stable prototropic tautomers of one of these molecules, the N6-cyclohexyl-N6-methyl-N2-phenyl-7H-purine-2,6-diamine (3), by Density Functional Theory (DFT) calculation in the gas phase, water and chloroform, the last solvent considered to give insights into the detection of broad signals in NMR analysis. In all cases the HN(9) tautomer resulted more stable than the HN(7) form, but the most stable conformations changed in different solvents. Molecules 1&ndash, 3 were evaluated on MCF-7 breast and HCT116 colorectal cancer cell lines showing that, while being less cytotoxic than reversine, they still caused cell cycle arrest in G2/M phase and polyploidy. Unlike reversine, which produced a pronounced cell cycle arrest in G2/M phase in all the cell lines used, similar concentrations of 1&ndash, 3 were effective only in cells where p53 was deleted or down-regulated. Therefore, our findings support a potential selective role of these structurally simplified, reversine-related molecules in p53-defective cancer cells.

Ultra-high performance liquid chromatography (UHPLC) coupled with diode array detection (DAD) was applied to improve separation and detection of mono- and bis-glucosyl esters of crocetin (crocins), the main red-colored constituents of saffron (Crocus sativus L.), and other polar components. Response surface methodology (RSM) was used to optimise the chromatographic resolution on the Kinetex C18 (Phenomenex) column taking into account of the combined effect of the column temperature, the eluent flow rate and the slope of a linear eluent concentration gradient. A three-level full-factorial design of experiments was adopted to identify suitable combinations of the above factors. The influence of the separation conditions on the resolutions of 22 adjacent peaks was simultaneously modelled by a multi-layer artificial neural network (ANN) in which a bit string representation was used to identify the target analytes. The chromatogram collected under the optimal separation conditions revealed a higher number of crocetin esters than those already characterised by means of mass-spectrometry data and usually detected by HPLC. Ultra-high performance liquid chromatography analyses carried out on the novel Luna Omega Polar C18 (Phenomenex) column confirmed the large number of crocetin derivatives. Further work is in progress to acquire mass-spectrometry data and to clarify the chemical structure to the newly found saffron components.

Previously tested n-hexane extracts of the Scorzonera latifolia showed promising bioactivity in vivo. Because triterpenes could account for this activity, n-hexane extracts were analyzed by HPLC to identify and quantify the triterpenes as the most abundant constituents. Other Scorzonera and Podospermum species, potentially containing triterpenic aglycones, were included in the study. An HPLC method for simultaneous determination of triterpene aglycones was therefore developed for analysis of Podospermum and Scorzonera species. n-Hexane extracts of root and aerial parts of S. latifolia, ten other Scorzonera species and two Podospermum species were studied to compare the content of triterpenes. HPLC was used for the qualitative and quantitative analysis of &alpha, amyrin, lupeol, lupeol acetate, taraxasteryl acetate, 3-&beta, hydroxy-fern-7-en-6-one acetate, urs-12-en-11-one-3-acetyl, 3-&beta, hydroxy-fern-8-en-7-one acetate, and olean-12-en-11-one-3-acetyl. Limits of detection and quantification were determined for each compound. HPLC fingerprinting of n-hexane extracts of Podospermum and Scorzonera species revealed relatively large amounts of triterpenes in a majority of investigated taxa. Lupeol, lupeol acetate, and taraxasteryl acetate were found in a majority of the species, except S. acuminata. The presence of &alpha, amyrin, 3&beta, hydroxy-fern-7-en-6-one-acetate, urs-12-en-11-one-3-acetyl, 3&beta, hydroxy-fern-8-en-7-one-acetate, and olean-12-en-11-one-3-acetyl was detected in varying amounts. The triterpene content could correlate with the analgesic and anti-inflammatory activity of Scorzonera, which was previously observed and Scorzonera species that have been determined to contain triterpenes in large amounts and have not yet been tested for their analgesic activity should be tested for their potential analgesic and anti-inflammatory potential. The presented HPLC method can be used for analysis of triterpene aglycones, for example dedicated to chemosystematic studies of the Scorzonerinae.

1-Alkylbenzenes as a precursor of surfactants, can be produced from ethylene, styrene, and hydrogen. These intermediates, lacking tertiary carbons, are environmentally more benign than commercial ones that bear the aromatic ring linked to an internal carbon of the aliphatic chain. The one-pot synthesis of highly linear 1-alkylbenzenes (LABs) through the homogeneous catalysis of olefin poly-insertion from cheap and largely available reagents can be carried out with a high turnover and selectivity. A purposely designed reactor that allows for the fine control of the three components feed, along with temperature, plays a key role in this achievement. A turnover of 194 g of LABs per mmol of catalyst per hour can be obtained with the simultaneous removal of polyethylene as a by-product.

Catenanes with desymmetrized ring components can undergo co-conformational rearrangements upon external stimulation and can form the basis for the development of molecular rotary motors. We describe the design, synthesis and properties of a [2]catenane consisting of a macrocycle—the ‘track’ ring—endowed with two distinct recognition sites (a bipyridinium and an ammonium) for a calix[6]arene—the ‘shuttle’ ring. By exploiting the ability of the calixarene to thread appropriate non-symmetric axles with directional selectivity, we assembled an oriented pseudorotaxane and converted it into the corresponding oriented catenane by intramolecular ring closing metathesis. Cyclic voltammetric experiments indicate that the calixarene wheel initially surrounds the bipyridinium site, moves away from it when it is reduced, and returns in the original position upon reoxidation. A comparison with appropriate model compounds shows that the presence of the ammonium station is necessary for the calixarene to leave the reduced bipyridinium site.

Compound libraries are important requirement in target-based drug discovery. In the present work, a small focused compound library based on β-aminoketone scaffold has been prepared combining microwave-assisted organic synthesis (MAOS) with polymer-assisted solution phase synthesis (PASPS) and replacing reaction workup standard purification procedures with solid phase extraction (SPE). Specifically, the effects of solvent, such as dioxane, dimethylformamide (DMF), polyethylene glycol 400 (PEG 400), temperature, irradiation time, stoichiometric ratio of reagents, and catalysts (HCl, acetic acid, cerium ammonium nitrate (CAN)) were investigated to maximize both conversion and yield. The optimized protocol generally afforded the desired products in satisfying yields and purities. The designed library is a part of our current research on sigma 1 receptor modulators, a valuable tool for the identification of novel potential hit compounds.

Cholesterylbutyrate (Chol-but) was chosen as a prodrug of butyric acid. Butyrate is not often used in vivo because its half-life is very short and therefore too large amounts of the drug would be necessary for its efficacy. In the last few years butyric acid's anti-inflammatory properties and its inhibitory activity towards histone deacetylases have been widely studied, mainly in vitro. Solid Lipid Nanoparticles (SLNs), whose lipid matrix is Chol-but, were prepared to evaluate the delivery system of Chol-but as a prodrug and to test its efficacy in vitro and in vivo. Chol-but SLNs were prepared using the microemulsion method; their average diameter is on the order of 100-150 nm and their shape is spherical. The antineoplastic effects of Chol-but SLNs were assessed in vitro on different cancer cell lines and in vivo on a rat intracerebral glioma model. The anti-inflammatory activity was evaluated on adhesion of polymorphonuclear cells to vascular endothelial cells. In the review we will present data on Chol-but SLNs in vitro and in vivo experiments, discussing the possible utilisation of nanoparticles for the delivery of prodrugs for neoplastic and chronic inflammatory diseases.

Metal oxide nanoparticles (NPs) are regarded as good candidates for many technological applications, where their functional environment is often an aqueous solution. The correct description of metal oxide electronic structure is still a challenge for local and semilocal density functionals, whereas hybrid functional methods provide an improved description, and local atomic function-based codes such as CRYSTAL17 outperform plane wave codes when it comes to hybrid functional calculations. However, the computational cost of hybrids are still prohibitive for systems of real sizes, in a real environment. Therefore, we here present and critically assess the accuracy of our electrostatic embedding quantum mechanical/molecular mechanical (QM/MM) coupling between CRYSTAL17 and AMBER16, and demonstrate some of its capabilities via the case study of TiO2 NPs in water. First, we produced new Lennard&ndash, Jones (LJ) parameters that improve the accuracy of water&ndash, water interactions in the B3LYP/TIP3P coupling. We found that optimizing LJ parameters based on water tri- to deca-mer clusters provides a less overstructured QM/MM liquid water description than when fitting LJ parameters only based on the water dimer. Then, we applied our QM/MM coupling methodology to describe the interaction of a 1 nm wide multilayer of water surrounding a spherical TiO2 nanoparticle (NP). Optimizing the QM/MM water&ndash, water parameters was found to have little to no effect on the local NP properties, which provide insights into the range of influence that can be attributed to the LJ term in the QM/MM coupling. The effect of adding additional water in an MM fashion on the geometry optimized nanoparticle structure is small, but more evident effects are seen in its electronic properties. We also show that there is good transferability of existing QM/MM LJ parameters for organic molecules&ndash, water interactions to our QM/MM implementation, even though these parameters were obtained with a different QM code and QM/MM implementation, but with the same functional.