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131.
Vincenzo Petrozza Antonio Carbone Teresa Bellissimo Natale Porta Giovanni Palleschi Antonio Luigi Pastore Angelina Di Carlo Carlo Della Rocca Francesco Fazi 《International journal of molecular sciences》2015,16(12):29219-29225
A key challenge for the improvement of clear cell renal cell carcinoma (ccRCC) management could derive from a deeper characterization of the biology of these neoplasms that could greatly improve the diagnosis, prognosis and treatment choice. The aim of this study was to identify specific miRNAs that are deregulated in tumor vs. normal kidney tissues and that could impact on the biology of ccRCC. To this end we selected four miRNAs (miR-21-5p, miR-210-3p, miR-185-5p and miR-221-3p) and their expression has been evaluated in a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) tissues from 20 ccRCC patients who underwent surgical nephrectomy resection. miR-21-5p and miR-210-3p resulted the most significantly up-regulated miRNAs in this patient cohort, highlighting these onco-miRNAs as possible relevant players involved in ccRCC tumorigenesis. Thus, this study reports the identification of specific oncogenic miRNAs that are altered in ccRCC tissues and suggests that they might be useful biomarkers in ccRCC management. 相似文献
132.
Ana Caroline Lustosa de Melo Carvalho Thiago de Sousa Fonseca Marcos Carlos de Mattos Maria da Concei??o Ferreira de Oliveira Telma Leda Gomes de Lemos Francesco Molinari Diego Romano Immacolata Serra 《International journal of molecular sciences》2015,16(12):29682-29716
Biocatalysis offers an alternative approach to conventional chemical processes for the production of single-isomer chiral drugs. Lipases are one of the most used enzymes in the synthesis of enantiomerically pure intermediates. The use of this type of enzyme is mainly due to the characteristics of their regio-, chemo- and enantioselectivity in the resolution process of racemates, without the use of cofactors. Moreover, this class of enzymes has generally excellent stability in the presence of organic solvents, facilitating the solubility of the organic substrate to be modified. Further improvements and new applications have been achieved in the syntheses of biologically active compounds catalyzed by lipases. This review critically reports and discusses examples from recent literature (2007 to mid-2015), concerning the synthesis of enantiomerically pure active pharmaceutical ingredients (APIs) and their intermediates in which the key step involves the action of a lipase. 相似文献
133.
Francesco Di Girolamo Andrea Masotti Isabella Lante Margherita Scapaticci Cosima Damiana Calvano Carlo Zambonin Maurizio Muraca Lorenza Putignani 《International journal of molecular sciences》2015,16(9):20896-20912
Extra virgin olive oil (EVOO) with its nutraceutical characteristics substantially contributes as a major nutrient to the health benefit of the Mediterranean diet. Unfortunately, the adulteration of EVOO with less expensive oils (e.g., peanut and corn oils), has become one of the biggest source of agricultural fraud in the European Union, with important health implications for consumers, mainly due to the introduction of seed oil-derived allergens causing, especially in children, severe food allergy phenomena. In this regard, revealing adulterations of EVOO is of fundamental importance for health care and prevention reasons, especially in children. To this aim, effective analytical methods to assess EVOO purity are necessary. Here, we propose a simple, rapid, robust and very sensitive method for non-specialized mass spectrometric laboratory, based on the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) coupled to unsupervised hierarchical clustering (UHC), principal component (PCA) and Pearson’s correlation analyses, to reveal corn oil (CO) adulterations in EVOO at very low levels (down to 0.5%). 相似文献
134.
Prof. Silvia Rivara Dr. Daniele Pala Dr. Alessio Lodola Prof. Marco Mor Dr. Valeria Lucini Dr. Silvana Dugnani Prof. Francesco Scaglione Dr. Annalida Bedini Dr. Simone Lucarini Prof. Giorgio Tarzia Prof. Gilberto Spadoni 《ChemMedChem》2012,7(11):1954-1964
The design of compounds selective for the MT1 melatonin receptor is still a challenging task owing to the limited knowledge of the structural features conferring selectivity for the MT1 subtype, and only few selective compounds have been reported so far. N‐(Anilinoalkyl)amides are a versatile class of melatonin receptor ligands that include nonselective MT1/MT2 agonists and MT2‐selective antagonists. We synthesized a new series of N‐(anilinoalkyl)amides bearing 3‐arylalkyloxy or 3‐alkyloxy substituents at the aniline ring, looking for new potent and MT1‐selective ligands. To evaluate the effect of substituent size and shape on binding affinity and intrinsic activity, both flexible and conformationally constrained derivatives were prepared. The phenylbutyloxy substituent gave the best result, providing the partial agonist 4 a , which was endowed with high MT1 binding affinity (pKi=8.93) and 78‐fold selectivity for the MT1 receptor. To investigate the molecular basis for agonist recognition, and to explain the role of the 3‐arylalkyloxy substituent, we built a homology model of the MT1 receptor based on the β2 adrenergic receptor crystal structure in its activated state. A binding mode for MT1 agonists is proposed, as well as a hypothesis regarding the receptor structural features responsible for MT1 selectivity of compounds with lipophilic arylalkyloxy substituents. 相似文献
135.
Angela Sciacqua Nadia Grillo Michele Quero Giorgio Sesti Francesco Perticone 《International journal of molecular sciences》2012,13(11):13804-13815
It is now well established that major risk factors for cardiovascular diseases (CVD) impact upon endothelial function by decreasing nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA), an endogenous analog of l-arginine, is able to inhibit the activity of endothelial-NO synthase, promoting endothelial dysfunction. Type 2 diabetes (T2D) is characterized by a reduced endothelium-dependent vasodilation and increased ADMA levels and ADMA is strongly associated with micro- and macrovascular diabetic complications. However, there are not a lot of data about the role of ADMA on endothelial function in newly diagnosed T2D patients without cardiovascular (CV) complications. For this aim, we have enrolled forty-five newly diagnosed T2D patients, evaluated by a oral glucose tolerance test, and thirty normal subjects. Endothelium-dependent and -independent vasodilatation was investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh) and sodium nitroprusside. ADMA was measured by high-performance liquid chromatography and insulin resistance (IR) by HOMA. Newly diagnosed T2D patients showed higher ADMA and l-arginine mean values in comparison with normal subjects and a significantly reduced ACh-stimulated forearm blood flow (FBF). In T2D patients FBF was significantly and inversely correlated with ADMA (r = −0.524, p < 0.0001) and in a multivariate regression analysis, ADMA resulted the stronger predictor of FBF, explaining the 27.5% of variability (p < 0.0001). In conclusion, ADMA was strongly related to endothelial dysfunction also in patients with newly diagnosed T2D, without clinically manifest vascular complications. This field is of great interest for understanding the mechanisms underlying the pathogenesis of diabetic disease and its CV complications. 相似文献
136.
Martino Colonna Corrado Berti Enrico Binassi Maurizio Fiorini Simone Sullalti Francesco Acquasanta Micaela Vannini Diana Di Gioia Irene Aloisio 《Polymer》2012,53(9):1823-1830
Imidazolium poly(butylene terephthalate) ionomers with ionic groups located randomly along the polymer chain or selectively as end-groups (telechelic) have been prepared in order to determine their antimicrobial (AM) activity. Two different approaches have been followed for the linkage of the imidazolium to the polymer backbone: a covalent bond and an ionic aggregation to sulfonated groups covalently bonded to the polymer. The ionic groups have been linked to the polymer in order to improve the long-term AM activity since the low molecular weight additives commonly used tends to migrate toward the surface during use. We have found that imidazolium ionomers present AM activity comparable with that of commercial antimicrobial agents such as Triclosan. The AM activity depends on the polymer architecture, the telechelic approach being more active compared to the random approach. We have proved that imidazolium ionomers retain their high AM activity even after 6 days in water at 60 °C while Triclosan consistently loses his activity. 相似文献
137.
Neil Gerard Quigley Dr. Stefano Tomassi Dr. Francesco Saverio di Leva Dr. Salvatore Di Maro Dr. Frauke Richter Dr. Katja Steiger Prof. Dr. Susanne Kossatz Prof. Dr. Luciana Marinelli Dr. Johannes Notni 《Chembiochem : a European journal of chemical biology》2020,21(19):2836-2843
αvβ6 Integrin is an epithelial transmembrane protein that recognizes latency-associated peptide (LAP) and primarily activates transforming growth factor beta (TGF-β). It is overexpressed in carcinomas (most notably, pancreatic) and other conditions associated with αvβ6 integrin-dependent TGF-β dysregulation, such as fibrosis. We have designed a trimeric Ga-68-labeled TRAP conjugate of the αvβ6-specific cyclic pentapeptide SDM17 (cyclo[RGD-Chg-E]-CONH2) to enhance αvβ6 integrin affinity as well as target-specific in-vivo uptake. Ga-68-TRAP(SDM17)3 showed a 28-fold higher αvβ6 affinity than the corresponding monomer Ga-68-NOTA-SDM17 (IC50 of 0.26 vs. 7.4 nM, respectively), a 13-fold higher IC50-based selectivity over the related integrin αvβ8 (factors of 662 vs. 49), and a threefold higher tumor uptake (2.1 vs. 0.66 %ID/g) in biodistribution experiments with H2009 tumor-bearing SCID mice. The remarkably high tumor/organ ratios (tumor-to-blood 11.2; -to-liver 8.7; -to-pancreas 29.7) enabled high-contrast tumor delineation in PET images. We conclude that Ga-68-TRAP(SDM17)3 holds promise for improved clinical PET diagnostics of carcinomas and fibrosis. 相似文献
138.
Annalisa MartucciLuisa Pasti Nicola MarchettiAlberto Cavazzini Francesco DondiAlberto Alberti 《Microporous and mesoporous materials》2012,148(1):174-183
The objectives of this study were to measure the sorption capacity of a dilute solution of drugs in water on hydrophobic zeolites and to quantify aspects of their adsorption mechanisms for potential use in wastewater remediation. The removal of three drugs, erythromycin (ERY), carbamazepine (CBZ) and levofloxacin (FLX) from water using three organophilic zeolites (Y, mordenite (MOR), ZSM-5) was investigated. Adsorption isotherms show that these three drugs are adsorbed in remarkable amounts by Y. These data were confirmed by thermogravimetric analysis. The presence of these drugs inside the Y cage was revealed by unit cell parameter variations and structural deformations obtained by X-ray structure analyses carried out using the Rietveld method on zeolite after adsorption. Our results indicate that the adsorption properties of zeolitic materials do not only depend on micropore size and that zeolite shape selectivity also depends on structural features which are difficult to determine “a priori”. In order to test the ability of organophilic zeolites in removing drugs from wastewater, the adsorption of ERY, FLX and CBZ on zeolite Y from water samples collected at the outlet of a wastewater treatment plant located in Northern Italy was determined. These drugs were almost completely adsorbed by Y zeolite, confirming that this material is suitable for removing drugs from wastewater. 相似文献
139.
Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily, interacts with its functional death receptors (DRs) and induces apoptosis in a wide range of cancer cell types. Therefore, TRAIL has been considered as an attractive agent for cancer therapy. However, many cancers are resistant to TRAIL-based therapies mainly due to the reduced expression of DRs and/or up-regulation of TRAIL pathway-related anti-apoptotic proteins. Compounds that revert such defects restore the sensitivity of cancer cells to TRAIL, suggesting that combined therapies could help manage neoplastic patients. In this article, we will focus on the TRAIL-sensitizing effects of natural products and synthetic compounds in colorectal cancer (CRC) cells and discuss the molecular mechanisms by which such agents enhance the response of CRC cells to TRAIL. 相似文献
140.
IB Spurr CN Birts F Cuda SJ Benkovic JP Blaydes A Tavassoli 《Chembiochem : a European journal of chemical biology》2012,13(11):1628-1634
Aminoimidazole carboxamide ribonucleotide transformylase/ inosine monophosphate cyclohydrolase (ATIC) is a bifunctional homodimeric enzyme that catalyzes the last two steps of de novo purine biosynthesis. Homodimerization of ATIC, a protein–protein interaction with an interface of over 5000 Å2, is required for its aminoimidazole carboxamide ribonucleotide (AICAR) transformylase activity, with the active sites forming at the interface of the interacting proteins. Here, we report the development of a small‐molecule inhibitor of AICAR transformylase that functions by preventing the homodimerization of ATIC. The compound is derived from a previously reported cyclic hexapeptide inhibitor of AICAR transformylase (with a Ki of 17 μM ), identified by high‐throughput screening. The active motif of the cyclic peptide is identified as an arginine‐tyrosine dipeptide, a capped analogue of which inhibits AICAR transformylase with a Ki value of 84 μM . A library of nonnatural analogues of this dipeptide was designed, synthesized, and assayed. The most potent compound inhibits AICAR transformylase with a Ki value of 685 nM , a 25‐fold improvement in activity from the parent cyclic peptide. The potential for this AICAR transformylase inhibitor in cancer therapy was assessed by studying its effect on the proliferation of a model breast cancer cell line. Using a nonradioactive proliferation assay and live cell imaging, a dose‐dependent reduction in cell numbers and cell division rates was observed in cells treated with our ATIC dimerization inhibitor. 相似文献