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991.
Paola Nicolini Michele M. Ciulla Gabriella Malfatto Carlo Abbate Daniela Mari Paolo D. Rossi Emanuela Pettenuzzo Fabio Magrini Dario Consonni Federico Lombardi 《PloS one》2014,9(5)
Background
Mild cognitive impairment (MCI) is set to become a major health problem with the exponential ageing of the world''s population. The association between MCI and autonomic dysfunction, supported by indirect evidence and rich with clinical implications in terms of progression to dementia and increased risk of mortality and falls, has never been specifically demonstrated.Aim
To conduct a comprehensive assessment of autonomic function in subjects with MCI by means of power spectral analysis (PSA) of heart rate variability (HRV) at rest and during provocative manoeuvres.Methods
This cross-sectional study involved 80 older outpatients (aged ≥65) consecutively referred to a geriatric unit and diagnosed with MCI or normal cognition (controls) based on neuropsychological testing. PSA was performed on 5-minute electrocardiographic recordings under three conditions—supine rest with free breathing (baseline), supine rest with paced breathing at 12 breaths/minute (parasympathetic stimulation), and active standing (orthosympathetic stimulation)—with particular focus on the changes from baseline to stimulation of indices of sympathovagal balance: normalized low frequency (LFn) and high frequency (HFn) powers and the LF/HF ratio. Blood pressure (BP) was measured at baseline and during standing. Given its exploratory nature in a clinical population the study included subjects on medications with a potential to affect HRV.Results
There were no significant differences in HRV indices between the two groups at baseline. MCI subjects exhibited smaller physiological changes in all three HRV indices during active standing, consistently with a dysfunction of the orthosympathetic system. Systolic BP after 10 minutes of standing was lower in MCI subjects, suggesting dysautonomia-related orthostatic BP dysregulation.Conclusions
Our study is novel in providing evidence of autonomic dysfunction in MCI. This is associated with orthostatic BP dysregulation and the ongoing follow-up of the study population will determine its prognostic relevance as a predictor of adverse health outcomes. 相似文献992.
Benedetta Apollonio Maria Teresa Sabrina Bertilaccio Umberto Restuccia Pamela Ranghetti Federica Barbaglio Paolo Ghia Federico Caligaris-Cappio Cristina Scielzo 《Journal of visualized experiments : JoVE》2014,(92)
The identification of molecules involved in tumor initiation and progression is fundamental for understanding disease’s biology and, as a consequence, for the clinical management of patients. In the present work we will describe an optimized proteomic approach for the identification of molecules involved in the progression of Chronic Lymphocytic Leukemia (CLL). In detail, leukemic cell lysates are resolved by 2-dimensional Electrophoresis (2DE) and visualized as “spots” on the 2DE gels. Comparative analysis of proteomic maps allows the identification of differentially expressed proteins (in terms of abundance and post-translational modifications) that are picked, isolated and identified by Mass Spectrometry (MS). The biological function of the identified candidates can be tested by different assays (i.e. migration, adhesion and F-actin polymerization), that we have optimized for primary leukemic cells. 相似文献
993.
994.
Emma Baglini Rahul Ravichandran Emanuela Berrino Silvia Salerno Elisabetta Barresi Anna Maria Marini Monica Viviano Sabrina Castellano Federico Da Settimo Claudiu T. Supuran Sandro Cosconati Sabrina Taliani 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1874
A library of variously decorated N-phenyl secondary sulphonamides featuring the bicyclic tetrahydroquinazole scaffold was synthesised and biologically evaluated for their inhibitory activity against human carbonic anhydrase (hCA) I, II, IV, and IX. Of note, several compounds were identified showing submicromolar potency and excellent selectivity for the tumour-related hCA IX isoform. Structure–activity relationship data attained for various substitutions were rationalised by molecular modelling studies in terms of both inhibitory activity and selectivity. 相似文献
995.
Mechanisms coupling cell cycle and cell fate operate at different steps during neural development. Intrinsic factors control the cell proliferation of distinct brain regions and changes of cell fate competence, whereas components of the cell cycle machinery could play a major role in setting the appropriate timing of the generation of different cell types. 相似文献
996.
Varnavas A Lassiani L Valenta V Berti F Mennuni L Makovec F 《Bioorganic & medicinal chemistry》2003,11(5):741-751
Having successfully obtained new CCK(1) ligands holding appropriate groups on the anthranilic acid dimer used as molecular scaffold we were interested in increasing their micromolar affinity for the CCK(1) receptors by modifying the spatial relationship of the main pharmacophoric groups. Since, we have proposed simplified analogues reducing the anthranilic acid dimer to a monomer. In this stage of our research program we have prepared and tested on CCK receptors a series of N-substituted anthranilic acid derivatives keeping a Phe residue at the C-terminal site. The indole-2-carbonyl group imparts the best CCK(1) receptor binding affinity (compound 1: IC(50)=197.5 nM) while a sharp decrease in binding affinity is observed for the other indole containing derivatives. Moreover, in order to support the different binding behaviour observed for the synthesized compounds, a conformational investigation was carried out. Finally, on the basis of the main pharmacophoric groups of the obtained new lead compound (1) (coded VL-0395) a receptor binding hypothesis has been provided. 相似文献
997.
Urszula Tylewicz Patrik Lundin Lorenzo Cocola Katarzyna Dymek Pietro Rocculi Sune Svanberg Petr Dejmek Federico G?mez Galindo 《Food biophysics》2012,7(1):28-34
The microstructure and the capillary pressure of the pore space are important variables for better understanding of the complex
phenomena occurring during vacuum impregnation (VI) of plant tissues. In this study, we used GASMAS (Gas in Scattering Media
Absorption Spectroscopy) of oxygen to, non-destructively, measure the dynamics of the internal pressure in apple pieces after
restoration of the atmospheric pressure. Apple pieces were impregnated with isotonic sucrose solution (18% w/v) at different
reduced pressures (15, 30, 45 kPa (abs.)). After restoration of the atmospheric pressure, the pressure of the remaining pore
space gas could remain as low as 50 kPa (abs) and rise slowly toward ambient over a time scale of hours. Both the residual
vacuum and the timescale of pressure equilibration with ambient varied with applied vacuum level and apple variety. It is
proposed that at least a part of the pore space of apples may be hydrophobic, giving rise to a negative Laplace pressure,
and thus the convective flow of impregnating solution is arrested at a mechanical equilibrium where internal pressure is lower
than external pressure. Further pressure equilibration can then only be achieved either by gas diffusion in gas phase, or
by gradual wetting of the pores. 相似文献
998.
Ryan M. McAdams Jeroen Vanderhoeven Richard P. Beyer Theo K. Bammler Federico M. Farin H. Denny Liggitt Raj P. Kapur Michael G. Gravett Craig E. Rubens Kristina M. Adams Waldorf 《PloS one》2012,7(10)
Background
Intrauterine exposure to amniotic fluid (AF) cytokines is thought to predispose to bronchopulmonary dysplasia (BPD). We evaluated the effects of GBS exposure on RNA expression in fetal lung tissue to determine early molecular pathways associated with fetal lung injury that may progress to BPD.Methods
Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received choriodecidual inoculation of either: 1) Group B Streptococcus (n = 5) or 2) saline (n = 5). Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. RNA was extracted from fetal lungs and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry.Results
Despite uterine quiescence in most cases, fetal lung injury occurred in four GBS cases (intra-alveolar neutrophils, interstitial thickening) and one control (peri-mortem hemorrhage). Significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6) were detected in GBS versus controls (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable by culture and PCR in the AF and fetal lungs. A total of 335 genes were differentially expressed greater than 1.5 fold (p<0.05) with GBS exposure associated with a striking upregulation of genes in innate and adaptive immunity and downregulation of pathways for angiogenesis, morphogenesis, and cellular growth and development.Conclusions
A transient choriodecidual infection may induce fetal lung injury with profound alterations in the genetic program of the fetal lung before signs of preterm labor. Our results provide a window for the first time into early molecular pathways disrupting fetal lung angiogenesis and morphogenesis before preterm labor occurs, which may set the stage for BPD. A strategy to prevent BPD should target the fetus in utero to attenuate alterations in the fetal lung genetic program. 相似文献999.
Antonella De Rosa Serena Pellegatta Marco Rossi Patrizia Tunici Letizia Magnoni Maria Carmela Speranza Federico Malusa Vincenzo Miragliotta Elisa Mori Gaetano Finocchiaro Annette Bakker 《PloS one》2012,7(12)
Glioblastoma multiforme (GBM) is among the most deadly cancers. A number of studies suggest that a fraction of tumor cells with stem cell features (Glioma Stem-like Cells, GSC) might be responsible for GBM recurrence and aggressiveness. GSC similarly to normal neural stem cells, can form neurospheres (NS) in vitro, and seem to mirror the genetic features of the original tumor better than glioma cells growing adherently in the presence of serum. Using cDNA microarray analysis we identified a number of relevant genes for glioma biology that are differentially expressed in adherent cells and neurospheres derived from the same tumor. Fatty acid-binding protein 7 (FABP7) was identified as one of the most highly expressed genes in NS compared to their adherent counterpart. We found that down-regulation of FABP7 expression in NS by small interfering RNAs significantly reduced cell proliferation and migration. We also evaluated the potential involvement of FABP7 in response to radiotherapy, as this treatment may cause increased tumor infiltration. Migration of irradiated NS was associated to increased expression of FABP7. In agreement with this, in vivo reduced tumorigenicity of GBM cells with down-regulated expression of FABP7 was associated to decreased expression of the migration marker doublecortin. Notably, we observed that PPAR antagonists affect FABP7 expression and decrease the migration capability of NS after irradiation. As a whole, the data emphasize the role of FABP7 expression in GBM migration and provide translational hints on the timing of treatment with anti-FABP7 agents like PPAR antagonists during GBM evolution. 相似文献
1000.
Matthias Seehase Jennifer J. P. Collins Elke Kuypers Reint K. Jellema Daan R. M. G. Ophelders Olga L. Ospina J. Perez-Gil Federico Bianco Raffaella Garzia Roberta Razzetti Boris W. Kramer 《PloS one》2012,7(10)