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991.
Daniela Caccamo Monica Currò Salvatore Condello Nadia Ferlazzo Riccardo Ientile 《Amino acids》2010,38(2):653-658
Proteolytic stress, resulting from the intracellular accumulation of misfolded or aggregated proteins, which exceed the capacity
of the ubiquitin–proteasome system to degrade them, plays a relevant role in neurodegenerative disorders, such as Alzheimer’s
disease, Parkinson’s disease, and Huntington’s chorea. Most of toxic protein aggregates are characterised by the presence
of isopeptide bonds (cross-links) catalysed by transglutaminase activity; further, several disease-specific proteins—tau,
amyloid-beta, alpha-synuclein, huntingtin—are in vitro and/or in vivo substrates of transglutaminase 2. These findings suggest
an important role for transglutaminase 2-mediated cross-linking reactions in neurodegeneration. Therefore, the use of transglutaminase
activity inhibitors could ameliorate neuronal cell death. New therapeutic perspectives also arise from the possibility to
prevent or reduce protein aggregation by enhancing the activation of heat shock proteins, which have been shown to be potent
suppressors of neurodegeneration in cell cultures/animal models. Interestingly, some heat shock proteins have been shown to
be in vitro or in vivo cross-linked by transglutaminase 2. These observations seem to suggest that transglutaminase activity
could be involved in the stabilization of intracellular protein aggregates by interfering with proteasomal degradation of
misfolded proteins. Further studies are needed to validate leading hypotheses and to open new prospects for developing therapeutic
tools. 相似文献
992.
993.
Simone Bertini Vincenzo Calderone Isabella Carboni Roberta Maffei Alma Martelli Adriano Martinelli Filippo Minutolo Mehdi Rajabi Lara Testai Tiziano Tuccinardi Riccardo Ghidoni Marco Macchia 《Bioorganic & medicinal chemistry》2010,18(18):6715-6724
New resveratrol (RES) analogs were developed by replacing the aromatic ‘core’ of our initial naphthalene-based RES analogs with pseudo-heterocyclic (salicylaldoxime) or heterocyclic (benzofuran, quinoline, and benzothiazole) scaffolds. The resulting analogs were tested for their antiproliferative and vasorelaxing effect, two typical properties shown by RES. Some of the new compounds confirmed strong antiproliferative activities, comparable to that previously found with the most active naphthalene-based analog. In particular, 3-(3,5-dihydroxyphenyl)-7-hydroxyquinoline exhibited the most potent antiproliferative effect (IC50 = 17.4 μM). In vascular assays, the highest levels of potency (pIC50 = 4.92) and efficacy (Emax = 88.2%) were obtained with 2-(3,5-dihydroxyphenyl)-6-hydroxybenzothiazole. A conformational analysis of these compounds indicated that the antiproliferative activity on MDA-MB-231 cancer cells can be correlated to a common sterical profile of the most active compounds and, in particular, to the spatial arrangement of the three phenolic groups. Furthermore, the vasorelaxing properties showed a good correlation with the electronic properties measured through the electrostatic molecular potential (ESP). 相似文献
994.
Marco L. Lolli Barbara Rolando Paolo Tosco Shilpi Chaurasia Antonella Di Stilo Loretta Lazzarato Eva Gorassini Riccardo Ferracini Simonetta Oliaro-Bosso Roberta Fruttero Alberto Gasco 《Bioorganic & medicinal chemistry》2010,18(7):2428-2438
A new series of bisphosphonates bearing either the nitrogen-containing NO-donor furoxan (1,2,5-oxadiazole 2-oxide) system or the related furazan (1,2,5-oxadiazole) in lateral chain has been developed. pKa values and affinity for hydroxyapatite were determined for all the compounds. The products were able to inhibit osteoclastogenesis on RAW 246.7 cells at 10 μM concentration. The most active compounds were further assayed on human PBMC cells and on rat microsomes. Unlike most nitrogen-containing bisphosphonates which target farnesyl pyrophosphate synthase, experimental and theoretical investigations suggest that the activity of our derivatives may be related to different mechanisms. The furoxan derivatives were also tested for their ability to relax rat aorta strips in view of their potential NO-dependent vasodilator properties. 相似文献
995.
Delineating Geographical Regions with Networks of Human Interactions in an Extensive Set of Countries 总被引:1,自引:0,他引:1
Stanislav Sobolevsky Michael Szell Riccardo Campari Thomas Couronné Zbigniew Smoreda Carlo Ratti 《PloS one》2013,8(12)
Large-scale networks of human interaction, in particular country-wide telephone call networks, can be used to redraw geographical maps by applying algorithms of topological community detection. The geographic projections of the emerging areas in a few recent studies on single regions have been suggested to share two distinct properties: first, they are cohesive, and second, they tend to closely follow socio-economic boundaries and are similar to existing political regions in size and number. Here we use an extended set of countries and clustering indices to quantify overlaps, providing ample additional evidence for these observations using phone data from countries of various scales across Europe, Asia, and Africa: France, the UK, Italy, Belgium, Portugal, Saudi Arabia, and Ivory Coast. In our analysis we use the known approach of partitioning country-wide networks, and an additional iterative partitioning of each of the first level communities into sub-communities, revealing that cohesiveness and matching of official regions can also be observed on a second level if spatial resolution of the data is high enough. The method has possible policy implications on the definition of the borderlines and sizes of administrative regions. 相似文献
996.
Paola Spessotto Antonella Zucchetto Massimo Degan Bruna Wasserman Carla Danussi Riccardo Bomben Roberto Perris Vincenzo Canzonieri Oriano Radillo Alfonso Colombatti Valter Gattei 《Matrix biology》2007,26(6):473-484
Cell adhesion and motility are central aspects in the pathophysiology of B cell chronic lymphocytic leukemia (B-CLL), but the role of specific extracellular matrix proteins is still to be completely unveiled. Purified peripheral blood neoplastic cells of B-CLL patients migrated poorly on laminins-111,-411,-511, but showed pronounced motility on laminin (LM)-332 in a high percentage of cases. B-CLL cell motility on LM-332 was mediated by the alpha3beta1 integrin and was preferentially observed in cells carrying a mutated IgV(H) gene profile. Within normal lymph nodes, LM-332 was circumscribed around blood vessels and to areas corresponding to marginal zones, where it was deposited in a pattern reminiscent of reticular fibers. Conversely, in B-CLL involved lymph nodes, a positive LM-332 reticular mesh was diffusely evident, throughout the disrupted nodal architecture. In the present study we identified LM-332 as a crucial motility-promoting factor for B-CLL lymphocytes and as a potential constituent favoring the dissemination of B-CLL lymphocytes through vascular basement membranes and possibly lymph node compartments. 相似文献
997.
Anna De Blasio Riccardo Di Fiore Giovanni Pratelli Rosa Drago-Ferrante Christian Saliba Shawn Baldacchino Godfrey Grech Christian Scerri Renza Vento Giovanni Tesoriere 《Journal of cellular physiology》2020,235(2):629-637
The present study shows that nuclear factor erythroid 2-related factor 2 (NRF2) and miR-29b-1-5p are two opposite forces which could regulate the fate of MDA-MB-231 cells, the most studied triple-negative breast cancer (TNBC) cell line. We show that NRF2 activation stimulates cell growth and markedly reduces reactive oxygen species (ROS) generation, whereas miR-29b-1-5p overexpression increases ROS generation and reduces cell proliferation. Moreover, NRF2 downregulates miR-29b-1-5p expression, whereas miR-29b-1-5p overexpression decreases p-AKT and p-NRF2. Furthermore, miR-29b-1-5p overexpression induces both inhibition of DNA N-methyltransferases (DNMT1, DNMT3A, and DNMT3B) expression and re-expression of HIN1, RASSF1A and CCND2. Conversely, NRF2 activation induces opposite effects. We also show that parthenolide, a naturally occurring small molecule, induces the expression of miR-29b-1-5p which could suppress NRF2 activation via AKT inhibition. Overall, this study uncovers a novel NRF2/miR-29b-1-5p/AKT regulatory loop that can regulate the fate (life/death) of MDA-MB-231 cells and suggests this loop as therapeutic target for TNBC. 相似文献
998.
Marianna Avitabile Vito Alessandro Lasorsa Sueva Cantalupo Antonella Cardinale Flora Cimmino Annalaura Montella Dalila Capasso Riccardo Haupt Loredana Amoroso Alberto Garaventa Alessandro Quattrone Maria Valeria Corrias Achille Iolascon Mario Capasso 《Journal of cellular and molecular medicine》2020,24(7):4072-4081
999.
Jesper B. Lund Shuxia Li Kaare Christensen Jonas Mengel‐From Mette Soerensen Riccardo E. Marioni John Starr Alison Pattie Ian J. Deary Jan Baumbach Qihua Tan 《Aging cell》2020,19(2)
The Y chromosome, a sex chromosome that only exists in males, has been ignored in traditional epigenetic association studies for multiple reasons. However, sex differences in aging‐related phenotypes and mortality could suggest a critical role of the sex chromosomes in the aging process. We obtained blood‐based DNA methylation data on the Y chromosome for 624 men from four cohorts and performed a chromosome‐wide epigenetic association analysis to detect Y‐linked CpGs differentially methylated over age and cross‐validated the significant CpGs in the four cohorts. We identified 40–219 significant CpG sites (false discovery rate <0.05) with >82% of them hypermethylated with increasing age, which is in strong contrast to the patterns reported on the autosomal chromosomes. Comparing the rate of change in the Y‐linked DNA methylation across cohorts that represent different age intervals revealed a trend of acceleration in DNA methylation with increasing age. The age‐dependent DNA methylation patterns on the Y chromosome were further examined for their association with all‐cause mortality with results suggesting that the predominant pattern of age‐related hypermethylation on the Y chromosome is associated with reduced risk of death. 相似文献
1000.
Giovanni Boano Irene Pellegrino Mauro Ferri Marco Cucco Fausto Minelli Susanne kesson 《Ecology and evolution》2020,10(14):7916-7928
Several species of migratory swifts breed in the Western Palearctic, but they differ in reproductive traits and nonbreeding areas explored in Africa. We examined survival and recapture probabilities of two species of swifts by capture–mark–recapture data collected in northern Italy (Pallid Swift Apus pallidus in Carmagnola, Turin, and Common Swift Apus apus in Guiglia, Modena) in the breeding season (May–July). Apparent survival rates were relatively high (>71%), comparable to other studies of European swifts, but showed marked annual variations. We used geolocators to establish the exact wintering areas of birds breeding in our study colonies. Common Swifts explored the Sahel zone during migration and spent the winter in SE Africa, while the Pallid Swifts remained in the Sahel zone for a longer time, shifting locations southeast down to Cameroun and Nigeria later in winter. These movements followed the seasonal rains from north to south (October to December). In both species, we found large yearly differences in survival probabilities related to different climatic indices. In the Pallid Swift, wintering in Western Africa, the Sahel rainfall index best explained survival, with driest seasons associated with reduced survival. In the Common Swift, wintering in SE Africa, the El Niño–Southern Oscillation (ENSO) cycle performed significantly better than Sahel rainfall or North Atlantic Oscillation (NAO). Extreme events and precipitation anomalies in Eastern Africa during La Niña events resulted in reduced survival probabilities in Common Swifts. Our study shows that the two species of swifts have similar average annual survival, but their survival varies between years and is strongly affected by different climatic drivers associated with their respective wintering areas. This finding could suggest important ecological diversification that should be taken into account when comparing survival and area use of similar species that migrate between temperate breeding areas and tropical wintering areas. 相似文献