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21.
Da Settimo F Primofiore G La Motta C Salerno S Novellino E Greco G Lavecchia A Laneri S Boldrini E 《Bioorganic & medicinal chemistry》2005,13(2):491-499
The 2,3-dihydrospiro[4H-thiopyrano[2,3-b]pyridin-4,4'-imidazolidine]-2',5'-dione 3 and its 7-methyl analogue 4 were synthesized and tested for their ability to inhibit aldose reductase (ALR2). To expand the structure-activity relationships, the sulfone 5 and the acetic acid derivative 7 were also prepared and tested. Compounds 3 and 4 proved to be potent ALR2 inhibitors, with IC50 values in the submicromolar range (0.96 and 0.94 microM, respectively) similar to that of sorbinil (0.65 microM). Moreover, compound 3 was found to be highly potent in preventing cataract development in severely galactosemic rats, like tolrestat, when administered as an eyedrop solution. Docking simulations of both R- and S-isomers of 3 into the ALR2 crystal structure were carried out to guide, prospectively, the design of new analogues. 相似文献
22.
Differential Effects of Human Immunodeficiency Virus Isolates on β-Chemokine and Gamma Interferon Production and on Cell Proliferation 下载免费PDF全文
Giampaolo Greco Sue H. Fujimura Dan V. Mourich Jay A. Levy 《Journal of virology》1999,73(2):1528-1534
All human immunodeficiency virus (HIV) isolates can grow readily in primary CD4+ T cells, but they can be distinguished by their ability to replicate in macrophages and established T-cell lines. The macrophage-tropic viruses are generally non-syncytium inducing (NSI), whereas the T-cell-line-tropic viruses are syncytium inducing (SI) in cultured cells. We now demonstrate that infection of CD4+ T cells by NSI and SI viruses shows a differential effect on production of β-chemokines and gamma interferon. Infection by NSI viruses increased production of MIP-1α, MIP-1β, and gamma interferon, whereas infection by SI viruses had no effect or decreased production of these cytokines. Production of RANTES was slightly increased during infection by both virus phenotypes. This differential effect of NSI and SI viruses was observed at the level of β-chemokine mRNA as well as at the level of protein expression. Infection by NSI viruses also increased CD4+ cell proliferation. These results may have relevance for a differential role of HIV strains in AIDS pathogenesis. 相似文献
23.
Intersection of mitochondrial fission and fusion machinery with apoptotic pathways: Role of Mcl‐1 下载免费PDF全文
Giampaolo Morciano Gaia Pedriali Luigi Sbano Tommaso Iannitti Carlotta Giorgi Paolo Pinton 《Biology of the cell / under the auspices of the European Cell Biology Organization》2016,108(10):279-293
Mitochondria actively contribute to apoptotic cell death through mechanisms including the loss of integrity of the outer mitochondrial membrane, the release of intermembrane space proteins, such as cytochrome c, in the cytosol and the caspase cascade activation. This process is the result of careful cooperation not only among members of the Bcl‐2 family but also dynamin‐related proteins. These events are often accompanied by fission of the organelle, thus linking mitochondrial dynamics to apoptosis. Emerging evidences are suggesting a fine regulation of mitochondrial morphology by Bcl‐2 family members and active participation of fission–fusion proteins in apoptosis. The debate whether in mitochondrial morphogenesis the role of Bcl‐2 family members is functionally distinct from their role in apoptosis is still open and, above all, which morphological changes are associated with cell death sensitisation. This review will cover the findings on how the mitochondrial fission and fusion machinery may intersect apoptotic pathways focusing on recent advances on the key role played by Mcl‐1. 相似文献
24.
Cascone T Morelli MP Morgillo F Kim WY Rodolico G Pepe S Tortora G Berrino L Lee HY Heymach JV Ciardiello F 《Journal of cellular physiology》2008,216(3):698-707
The proteasome plays a pivotal role in the turnover of regulatory transduction proteins induced by activated cell membrane growth factor receptors. The epidermal growth factor receptor (EGFR) pathway is crucial in the development and progression of human epithelial cancers. Proteasome inhibition may sensitize human cancer cell lines to EGFR inhibitors. We investigated the growth inhibitory and pro-apoptotic effects of the proteasome inhibitor bortezomib in combination with anti-EGFR drugs, such as gefitinib, vandetanib, and cetuximab in EGFR-expressing human cancer cell lines. Bortezomib determined dose-dependent growth inhibition in a nine cancer cell line panel (IC(50) values, range 6-42 nM). A significant synergistic growth inhibitory effect was observed with the combination of bortezomib and each EGFR inhibitor in all cell lines (combination index, CI, range 0.10-0.55), which was accompanied by a significant induction in apoptosis by the combined treatment with bortezomib, cetuximab and vandetanib. In HCT-116 colon cancer and A549 lung adenocarcinoma cells, bortezomib plus EGFR inhibitor treatment induced a more effective inhibition of EGFR-activated down-stream signals, including a marked suppression in activated, phosphorylated Akt (P-Akt). In contrast, overexpression of a constitutively active P-Akt protected A549 cells by cell growth inhibition and apoptosis following treatment with bortezomib and EGFR inhibitors. The combined treatment with bortezomib and EGFR inhibitors has a synergistic growth inhibitory and pro-apoptotic activity in different human cancer cells which possess a functional EGFR-dependent autocrine growth pathway through to a more efficient and sustained inhibition of Akt. 相似文献
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Paolo Paoli Francesca Sbrana Anna Caselli Paolo Cirri Lucia Formigli Giampaolo Manao Giampietro Ramponi 《Journal of molecular biology》2010,400(4):889-907
Previous works reported that a mild increase in homocysteine level is a risk factor for cardiovascular and neurodegenerative diseases in humans. Homocysteine thiolactone is a cyclic thioester, most of which is produced by an error-editing function of methionyl-tRNA synthetase, causing in vivo post-translational protein modifications by reacting with the ?-amino group of lysine residues. In cells, the rate of homocysteine thiolactone synthesis is strictly dependent on the levels of the precursor metabolite, homocysteine. In this work, using bovine serum albumin as a model, we investigated the impact of N-homocysteinylation on protein conformation as well as its cellular actions. Previous works demonstrated that protein N-homocysteinylation causes enzyme inactivation, protein aggregation, and precipitation. In addition, in the last few years, several pieces of evidence have indicated that protein unfolding and aggregation are crucial events leading to the formation of amyloid fibrils associated with a wide range of human pathologies. For the first time, our results reveal how the low level of protein N-homocysteinylation can induce mild conformational changes leading to the formation of native-like aggregates evolving over time, producing amyloid-like structures. Taking into account the fact that in humans about 70% of circulating homocysteine is N-linked to blood proteins such as serum albumin and hemoglobin, the results reported in this article could have pathophysiological relevance and could contribute to clarify the mechanisms underlying some pathological consequences described in patients affected by hyperhomocysteinemia. 相似文献
28.
Francesca Gherardi Sandro Bertolino Marco Bodon Sandra Casellato Simone Cianfanelli Marco Ferraguti Elisabetta Lori Graziella Mura Annamaria Nocita Nicoletta Riccardi Giampaolo Rossetti Emilia Rota Riccardo Scalera Sergio Zerunian Elena Tricarico 《Biological invasions》2008,10(4):435-454
The paper provides a list of the non-indigenous animal species occurring today in Italian inland waters. Xenodiversity was
found to amount to 112 species (64 invertebrates and 48 vertebrates), which contribute for about 2% to the inland-water fauna
in Italy. Northern and central regions are most affected, and Asia, North America, and the rest of Europe are the main donor
continents. The large majority of non-indigenous species entered Italy as a direct or indirect effect of human intervention.
A difference between invertebrates and vertebrates was found for their mode of arrival (unintentional for invertebrates and
intentional for vertebrates). Accidental transport, in association with both fish (for aquaculture or stock enhancement) and
crops, has been the main vector of invertebrate introductions, whereas vertebrates were mostly released for stocking purposes.
Overall stock enhancement (47.92%) and culture (37.5%) prevailed over the other pathways. Seventeen and 7 species of our list
are included among the 100 worst invasive species of Europe (DAISIE) and of the world (IUCN), respectively. For some (but
not all) non-indigenous species recorded in Italy the multilevel impact exerted on the recipient communities and ecosystems
is known, even if rarely quantified, but knowledge on their chronic impact is still missing. Additional research is needed
to provide criteria for prioritizing intervention against well established invaders and identify which new potential invader
should be targeted as “unwanted”. 相似文献
29.
Mariagiuseppina Pellegrini Barbara Manconi Alessandra Olianas Maria Teresa Sanna Claudia Meloni Monica Pirastru Paolo Mereu Giovanni Leoni Bruno Masala Laura Manca 《Biochimica et Biophysica Acta (BBA)/General Subjects》2011
Background
HbF-Monserrato-Sassari is a newly discovered abnormal fetal hemoglobin observed in an apparently normal newborn baby during a hemoglobinopathies survey at birth in North Sardinian population.Methods
Electrophoretic analysis of the cord blood lysate evidenced for an abnormal tetramer due to a mutated fetal globin chain. Electrospray ionisation-mass spectrometry and gene sequencing were used to identify the mutation. Oxygen binding ability of the variant Hb was determined.Results
Sequencing of the γ globin genes revealed the TGT → CGT transition at codon 93 in one of the two Gγ genes, which leads to the Arg for Cys amino acid replacement at position 9 of the F α-helix. The amino acid substitution was confirmed by mass spectrometric analysis of the globin chains. Since modifications or substitutions at position β93 are known to affect the arrangement of a salt bridge at the α1β2 sliding contacts that are crucial for subunit cooperativity, the functional properties of the variant were studied to evaluate the effect of the replacement at the same position in the γ globin chain. With respect to normal HbF, the variant showed a significant increase in oxygen affinity and a slight decrease of both Bohr effect and cooperativity.General significance
Result indicates a key role of the Cys γ93 residue for subunit cooperativity in the T → R transition of the HbF tetramer. Substitutions at the F9 position of the Gγ globin may result in stabilization of the high affinity R-state of the Hb tetramer. Because of the loss of Cys γ93 residue, this variant is considered to be potentially compromised in nitric oxide transport. 相似文献30.
Andy F.S. Taylor Alan E. Hills Giampaolo Simonini Ernst E. Both Ursula Eberhardt 《Mycological Research》2006,110(3):276-287
Identification of species within the boletoid genus Xerocomus has relied heavily upon the macromorphological features of the basidiomes. However, the phenotypic plasticity of these features has resulted in considerable confusion over the delimitation of taxa. In this study, we examined collections attributed to the X. subtomentosus complex in Europe using morphological and rDNA–ITS sequence data. In total, 45 European collections from a wide range of geographical areas and ecological conditions were included in the study. In spite of detecting considerable genetic variation, even within individual basidiomes of X. subtomentosus, molecular data, spore size, flesh colour, and the colour of the basal mycelium allow for the recognition of four distinct taxa: two correspond to X. subtomentosus (13 collections) and X. ferrugineus (20); one X. chrysonemus sp. nov. (10), to date only found in the UK, is described as new; and the existence of another taxon (two; Italy and UK) is noted but left undescribed owing to lack of material. Eight collections from North America were also included in the study, from which two taxa with a close affinity to X. ferrugineus were recognised. 相似文献