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101.
Giovanni?AppendinoEmail author Alberto?Minassi Nives?Daddario 《Phytochemistry Reviews》2005,4(1):3-10
The shift in nutritional sciences from survival and safety to the promotion of well-being has led to systematic investigations on the biological activity of natural products of dietary origin, questioning the assumption that food plants contain little if any secondary metabolites apart those revealed by our senses and responsible for their colour, taste, and flavour. With 25% of the human population consuming chilli pepper every day, capsaicin is the most important pharmacological agent we get from our diet, and the study of its pungency set in motion a multidisciplinary investigation that ultimately led to the discovery of vanilloid receptors (TRPVs), a class of ion channels involved in thermo-, chemo-, and mechanosensation, and whose malfunctioning is implicated in neurogenic inflammation and a host of other pathological conditions. A series of studies centred on the modification of capsaicin will be described, focusing on a) the preparation of a library of unnatural natural capsaicinoids and the identification of leads with the lipophilic C-moiety amenable to structure-activity study, and b) the reversal of the biological activity of capsaicin from a TRPV1 agonist into an antagonist by modification of its vanillyl moiety. 相似文献
102.
Yeast cells expressing the Glu418Lys human topoisomerase I mutant display a camptothecin resistance that slowly decreases as a function of time. Molecular characterization of the single steps of the catalytic cycle of the purified mutant indicates that it has a relaxation activity identical to the wild-type protein but a different DNA sequence specificity for the cleavage sites when compared to the wild-type enzyme, as assayed on several substrates. In particular the mutant has a low specificity for CPT sensitive cleavable sites. In fact, the mutant has, at variance of the wild-type enzyme, a reduced preference for cleavage sites having a thymine base in position −1 of the scissile strand. This preference, together with the strict requirement for a thymine base in position −1 for an efficient camptothecin binding, explains the temporary camptothecin resistance of the yeast cell expressing the mutant and points out the importance of the DNA sequence in the binding of the camptothecin drug. 相似文献
103.
Dondero F Jonsson H Rebelo M Pesce G Berti E Pons G Viarengo A 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2006,143(2):150-157
Amoebic Dictyostelium discoideum cells were employed in a bioassay to evaluate stress responses after exposures to the polyaromatic hydrocarbon benzo[a]pyrene (B[a]P) and two heavy metals (copper and mercury). Furthermore, we developed a recombinant cell line expressing a labile Green Fluorescent Protein (GFP) variant expressed under the control of an actin promoter to monitor stress-related protein degradation. Finally, cell viability was monitored to discriminate lethal exposure concentrations. The results demonstrated that exposure to sub-micromolar concentrations of mercury rendered significant changes in all studied physiological parameters, whereas B[a]P became toxic at low micromolar, and copper at high micromolar concentrations. Exposure to 0.5 microM mercury significantly reduced lysosomal membrane stability (LMS), endocytosis rate, GFP expression, and further resulted in the elevation of cytosolic free Ca(2+) ([Ca(2+)](i)). LMS in mercury-treated cells that had been pre-incubated with a specific Ca(2+)-dependent phospholipase A2 blocking agent was however not affected by the exposure, indicating that the toxic action of mercury is linked to the activation of phospholipase A2 via a Ca(2+)-signaling pathway. Exposure to 20 microM B[a]P significantly reduced LMS, endocytosis rate, and GFP expression, however without affecting [Ca(2+)](i), suggesting a calcium-independent route of toxicity for this compound. None of the physiological parameters were significantly affected by copper exposure at concentrations <400 microM, demonstrating a high resistance to this metal. Our results further showed that neither cell growth nor viability was affected by concentrations altering the studied physiological parameters. LMS, endocytosis rate, and [Ca(2+)](I), therefore, appear sensitive biomarkers of pollutant-related stress in amoebic cells. 相似文献
104.
Blanco A Simeone R Cenci A Gadaleta A Tanzarella OA Porceddu E Salvi S Tuberosa R Figliuolo G Spagnoletti P Röder MS Korzun V 《Cellular & molecular biology letters》2004,9(3):529-541
A set of recombinant inbred lines (RIL) derived from a cross between the cultivar Messapia of durum wheat (Triticum turgidum var. durum) and the accession MG4343 of T. turgidum var. dicoccoides was analysed to increase the number of assigned markers and the resolution of the previously constructed genetic linkage map. An updated map of the durum wheat genome consisting of 458 loci was constructed. These loci include 261 Restriction Fragment Length Polymorphisms (RFLPs), 91 microsatellites (Simple Sequence Repeats, SSRs), 87 Amplified Fragment Length Polymorphisms (AFLPs), two ribosomal genes, and nine biochemical (seven seed storage proteins and two isozymes) and eight morphological markers. The loci were mapped on all 14 chromosomes of the A and B genomes, and covered a total distance of 3038.4 cM with an average distance of 6.7 cM between adjacent markers. The molecular markers were evenly distributed between the A and the B genomes (240 and 218 markers, respectively). An additional forty loci (8.8%) could not be assigned to a specific linkage group. A fraction (16.4%) of the markers significantly deviated from the expected Mendelian ratios; clusters of loci showing distorted segregation were found on the 1B, 2A, 2B, 3A, 4A, 7A and 7B chromosomes. The genetic lengths of the chromosomes range from 148.8 cM (chromosome 6B) to 318.0 cM (chromosome 2B) and approximately concur with their physical lengths. Chromosome 2B has the largest number of markers (47), while the chromosomes with the fewest markers are 3A and 6B (23). There are two gaps larger than 40 cM on chromosomes 2A and 3B. The durum wheat map was compared with the published maps of bread and durum wheats; the order of most common RFLP and SSR markers on the 14 chromosomes of the A and B genomes were nearly identical. A core-map can be extracted from the high-density Messapia x dicoccoides map and a subset of uniformly distributed markers can be used to detect and map quantitative trait loci. 相似文献
105.
Pasquale Petrilli Pietro Pucci Anna Maria Garzillo Giovanni Sannia Dr. Gennaro Marino 《Molecular and cellular biochemistry》1981,35(2):121-128
Summary Reactivity of sulphydryl groups of cytosolic and mitochondrial aspartate aminotransferases from ox heart has been studied.
A total of 5 and 7 cysteine residues per monomer are present in cAATo and mAATo, respectively. In native conditions only a
single sulphydryl group can be titrated by Nbs2 while the catalytic activity remains unchanged, however in the mitochondrial isozyme the reactivity depends on the functional
state of the enzyme. Reactivity toward NEM reveals the existence of a syncatalytic sulphydryl group in the cytosolic isozyme.
Titration of cAATo with pMB at pH 8 and pH 5 confirms the existence of two exposed sulphydryl groups with a different reactivity.
The results compared with those reported on the corresponding isozymes from pig and chicken heart show that syncatalytic sulphydryl
groups are of general occurrence in these enzymes. 相似文献
106.
Pasqualina Woodrow Giovanni Pontecorvo Stefania Fantaccione Amodio Fuggi Ioannis Kafantaris Danila Parisi Petronia Carillo 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,121(2):311-322
Long terminal repeat retrotransposons are the most abundant mobile elements in the plant genome and play an important role in the genome reorganization induced by environmental challenges. Their success depends on the ability of their promoters to respond to different signaling pathways that regulate plant adaptation to biotic and abiotic stresses. We have isolated a new Ty1-copia-like retrotransposon, named Ttd1a from the Triticum durum L. genome. To get insight into stress activation pathways in Ttd1a, we investigated the effect of salt and light stresses by RT-PCR and S-SAP profiling. We screened for Ttd1a insertion polymorphisms in plants grown to stress and showed that one new insertion was located near the resistance gene. Our analysis showed that the activation and mobilization of Ttd1a was controlled by salt and light stresses, which strengthened the hypothesis that stress mobilization of this element might play a role in the defense response to environmental stresses. 相似文献
107.
Silvia De Francia Antonio D’Avolio Francesca De Martino Elisa Pirro Lorena Baietto Marco Siccardi Marco Simiele Silvia Racca Giuseppe Saglio Francesco Di Carlo Giovanni Di Perri 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2009,877(18-19):1721-1726
A new method using high performance liquid chromatography coupled with electrospray mass spectrometry is described for the quantification of plasma concentration of tyrosine kinase inhibitors imatinib, dasatinib and nilotinib. A simple protein precipitation extraction procedure was applied on 250 μl of plasma aliquots. Chromatographic separation of drugs and Internal Standard (quinoxaline) was achieved with a gradient (acetonitrile and water + formic acid 0.05%) on a C18 reverse phase analytical column with 20 min of analytical run, at flow rate of 1 ml/min. Mean intra-day and inter-day precision for all compounds were 4.3 and 11.4%; mean accuracy was 1.5%; extraction recovery ranged within 95 and 114%. Calibration curves ranged from 10,000 to 62.5 ng/ml. The limit of quantification was set at 78.1 ng/ml for imatinib and at 62.5 ng/ml for dasatinib and nilotinib. This novel developed methodology allows a specific, sensitive and reliable simultaneous determination of the three tyrosine kinase inhibitors imatinib, dasatinib and nilotinib in a single chromatographic run, useful for drugs estimation in plasma of patients affected by chronic myeloid leukemia. 相似文献
108.
Marra M Salzano G Leonetti C Porru M Franco R Zappavigna S Liguori G Botti G Chieffi P Lamberti M Vitale G Abbruzzese A La Rotonda MI De Rosa G Caraglia M 《Biotechnology advances》2012,30(1):302-309
Zoledronic acid (ZOL) is a drug whose potent anti-cancer activity is limited by its short plasma half-life and rapid uptake and accumulation within bone. We have recently proposed new delivery systems to avoid ZOL accumulation into the bone, thus improving extra-skeletal bioavailability. In this work, we have compared the technological and anti-cancer features of either ZOL-containing self-assembly PEGylated nanoparticles (NPs) or ZOL-encapsulating PEGylated liposomes (LIPO-ZOL). ZOL-containing NPs showed superior technological characteristics in terms of mean diameter, size distribution, and ZOL encapsulation efficiency, compared to LIPO-ZOL. Moreover, the anti-cancer activity of NPs in nude mice xenografted with prostate cancer PC3 cells was higher than that one induced by LIPO-ZOL. In addition, NPs induced the complete remission of tumour xenografts and an increase of survival time higher than that one observed with LIPO-ZOL. It has also to be considered that PC3 tumour xenografts were almost completely resistant to the anti-cancer effects induced by free ZOL. Both nanotechnological products did not induce toxic effects not affecting the mice weight nor inducing deaths. Moreover, the histological examination of some vital organs such as liver, kidney and spleen did not find any changes in terms of necrotic effects or modifications in the inflammatory infiltrate. On the other hand, NPs but not LIPO-ZOL caused a statistically significant reduction of the tumour associated macrophages (TAM) in tumour xenografts. This effect was paralleled by a significant increase of both necrotic and apoptotic indexes. The effects of the NPs were also higher in terms of neo-angiogenesis inhibition. These results suggest the future preclinical development of ZOL-encapsulating NPs in the treatment of human cancer. 相似文献
109.
Aliaksei?Kisialiou Giordana?Pelone Albino?Carrizzo Giovanni?Grillea Valentina?Trimarco Marina?Marino Michelangelo?Bartolo Alessandro?Marco?De Nunzio Rodolfo?Grella Alessandro?Landolfi Annibale?Puca Claudio?Colonnese Carmine?VecchioneEmail author 《Immunity & ageing : I & A》2012,9(1):22
Background
Thrombolytic therapy (TT) for acute ischemic stroke (AIS) can provoke bleeding’s complication depending on the ischemic lesion (IL) dimension. Inflammation involved in the setting of acute ischaemic stroke, is associated with infarct size. We aimed to study the independent correlation and association between clinical panel of routinely identified biomarkers, including inflammatory parameters, and cerebral IL dimension and site.Results
We evaluated eleven biomarkers in 105 unrelated patients during their hospitalization after acute stroke event. Our data indicate a significant association of: a) confluent IL size with 4th quartile of Erythrocyte Sedimentation Rate (ESR) (OR = 5.250; 95% CI, 1.002 to 27.514) and an independent correlation with sex; b) confluent IL size with 3rd quartile of fibrinogen (OR = 5.5; 95% CI, 1.027 to 29.451); c) confluent IL size with 3rd quartile of platelets (OR= 0.059; 95% CI, 0.003 to 1.175) and independent correlation with sex; d) smaller IL size (OR = 5.25; 95% CI, 1.351 to 20.396) with 3rd quartile of albumin levels and nodular and parenchimal IL size with 2nd (OR = 0.227; 95% CI, 0.053 to 0.981), 3rd (OR = 0.164; 95% CI, 0.038 to 0.711) and 4th (OR = 0.205; 95% CI, 0.048 to 0.870) quartiles albumin levels; e) smaller IL size with 3rd quartile triglycerides (TG) levels (OR = 9; 95% CI, 2.487 to 32.567) and an independent correlation with anterior location. Smaller IL size, anterior AIS turned out to be independently correlated with high serum albumin levels. Finally, high INR and PTT values were associated with worse NIHSS clinical outcomes in contrast to that observed with higher albumin level.Conclusions
We provide evidence of routine biomarkers levels correlation with acute IL size, independently of age and sex. In addition, we highlight the importance of differentiation of biomarkers normal interval levels for further improvement not only of the clinical decision making but also in post-acute clinical outcome management.110.
Claire Booyjz̈sen Charlotte A. Scarff Ben Moreton Ian Portman James H. Scrivens Giovanni Costantini Peter J. Sadler 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012,1820(3):427-436
BackgroundThe nature of fibrillar deposits from aqueous solutions of human serum and recombinant human transferrin on mica and carbon-coated formvar surfaces has been investigated.Methods and ResultsAtomic force microscopy showed that the deposition of recombinant transferrin onto the hydrophilic surface of mica resulted in the formation of a monolayer-thick film composed of conformationally-strained flattened protein molecules. Elongated fibres developed on top of this layer and appeared to be composed of single proteins or small clusters thereof. Monomeric and dimeric transferrins were separated by gel permeation chromatography and their states of aggregation confirmed by mass spectrometry and dynamic light scattering. Transmission electron-microscopy showed that dimeric transferrin, but not monomeric transferrin, deposited on carbon-coated formvar grids forms rounded (circular) structures ca. 250 nm in diameter. Small transferrin fibrils ca. 250 nm long appeared to be composed of smaller rounded sub-units. Synchrotron radiation-circular dichroism and, Congo red and thioflavin-T dye-binding experiments suggested that transferrin aggregation in solution does not involve major structural changes to the protein or formation of classical β-sheet amyloid structures. Collisional cross sections determined via ion mobility–mass spectrometry showed little difference between the overall protein shapes of apo- and holo-transferrin in the gas phase.General significanceThe possibility that transferrin deformation and aggregation are involved in neurological disorders such as Parkinson's and Alzheimer's disease is discussed. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders. 相似文献