135 results on '"Fiordaliso, F"'
Search Results
2. Protective effect of the tunneling nanotube-TNFAIP2/M-sec system on podocyte autophagy in diabetic nephropathy.
- Author
-
Barutta, F., Bellini, S., Kimura, S., Hase, K., Corbetta, B., Corbelli, A., Fiordaliso, F., Bruno, S., Biancone, L., Barreca, A., Papotti, M.G., Hirsh, E., Martini, M., Gambino, R., Durazzo, M., Ohno, H., and Gruden, G.
- Subjects
LYSOSOMES ,DIABETIC nephropathies ,ADVANCED glycation end-products ,RECEPTOR for advanced glycation end products (RAGE) ,TUMOR necrosis factors ,FOCAL segmental glomerulosclerosis ,MEMBRANE proteins ,HYPERGLYCEMIA - Abstract
Podocyte injury leading to albuminuria is a characteristic feature of diabetic nephropathy (DN). Hyperglycemia and advanced glycation end products (AGEs) are major determinants of DN. However, the underlying mechanisms of podocyte injury remain poorly understood. The cytosolic protein TNFAIP2/M-Sec is required for tunneling nanotubes (TNTs) formation, which are membrane channels that transiently connect cells, allowing organelle transfer. Podocytes express TNFAIP2 and form TNTs, but the potential relevance of the TNFAIP2-TNT system in DN is unknown. We studied TNFAIP2 expression in both human and experimental DN and the renal effect of tnfaip2 deletion in streptozotocin-induced DN. Moreover, we explored the role of the TNFAIP2-TNT system in podocytes exposed to diabetes-related insults. TNFAIP2 was overexpressed by podocytes in both human and experimental DN and exposre of podocytes to high glucose and AGEs induced the TNFAIP2-TNT system. In diabetic mice, tnfaip2 deletion exacerbated albuminuria, renal function loss, podocyte injury, and mesangial expansion. Moreover, blockade of the autophagic flux due to lysosomal dysfunction was observed in diabetes-injured podocytes both in vitro and in vivo and exacerbated by tnfaip2 deletion. TNTs allowed autophagosome and lysosome exchange between podocytes, thereby ameliorating AGE-induced lysosomal dysfunction and apoptosis. This protective effect was abolished by tnfaip2 deletion, TNT inhibition, and donor cell lysosome damage. By contrast, Tnfaip2 overexpression enhanced TNT-mediated transfer and prevented AGE-induced autophagy and lysosome dysfunction and apoptosis. In conclusion, TNFAIP2 plays an important protective role in podocytes in the context of DN by allowing TNT-mediated autophagosome and lysosome exchange and may represent a novel druggable target. Abbreviations: AGEs: advanced glycation end products; AKT1: AKT serine/threonine kinase 1; AO: acridine orange; ALs: autolysosomes; APs: autophagosomes; BM: bone marrow; BSA: bovine serum albumin; CTSD: cathepsin D; DIC: differential interference contrast; DN: diabetic nephropathy; FSGS: focal segmental glomerulosclerosis; HG: high glucose; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; LMP: lysosomal membrane permeabilization; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PI3K: phosphoinositide 3-kinase; STZ: streptozotocin; TNF: tumor necrosis factor; TNFAIP2: tumor necrosis factor, alpha-induced protein 2; TNTs: tunneling nanotubes; WT: wild type. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
3. A morphological classification of the fat particles found in the urinary sediment of patients with Fabry disease
- Author
-
Fogazzi, G, Garigali, G, Pieruzzi, F, Corbelli, A, Fiordaliso, F, Consonni, D, Messa, P, Fogazzi, Giovanni B, Garigali, Giuseppe, Pieruzzi, Federico, Corbelli, Alessandro, Fiordaliso, Fabio, Consonni, Dario, Messa, Piergiorgio, Fogazzi, G, Garigali, G, Pieruzzi, F, Corbelli, A, Fiordaliso, F, Consonni, D, Messa, P, Fogazzi, Giovanni B, Garigali, Giuseppe, Pieruzzi, Federico, Corbelli, Alessandro, Fiordaliso, Fabio, Consonni, Dario, and Messa, Piergiorgio
- Abstract
Objectives: The search in the urinary sediment (U-sed) of fat particles with peculiar morphology is a simple and inexpensive tool for the diagnosis of Fabry disease (FD) nephropathy. In this study we investigated the morphology of a high number of such fat particles with the aim to obtain a morphological classification to be used for their identification. Methods: Study of the morphology of fat particles in the U-sed of a cohort of FD patients using: Bright field plus phase contrast microscopy (BF + PC), polarized light microscopy (POL), and transmission electron microscopy (TEM). Comparison of these results with those obtained for the fat particles seen in the U-sed of a control group (CG) of patients with non-FD glomerulopathies. Results: FD: 18 U-sed from six patients (three samples/patient) were prospectively investigated and 506 fat particles identified. With BF + PC, these were classified in eight morphological categories (seven of which were confirmed by TEM), and with POL in 10 others. CG: Eight U-sed from eight patients were investigated and 281 fat particles identified. These fell into four BF + PC morphological categories and into eight POL categories. While some categories were significantly more frequent in FD others were more frequent in the CG. Conclusions: Our study demonstrates that 1. The morphology of fat particles found in the U-sed of FD patients is much wider and complex than that described so far 2. Several significant differences exist in the morphology of such fat particles between FD and CG patients.
- Published
- 2021
4. Mitochondrial structural alterations in ovarian cancer patient-derived xenografts resistant to cisplatin
- Author
-
Ricci, F, Corbelli, A, Affatato, R, Chilà, R, Chiappa, M, Brunelli, L, Fruscio, R, Pastorelli, R, Fiordaliso, F, Damia, G, Ricci, Francesca, Corbelli, Alessandro, Affatato, Roberta, Chilà, Rosaria, Chiappa, Michela, Brunelli, Laura, Fruscio, Robert, Pastorelli, Roberta, Fiordaliso, Fabio, Damia, Giovanna, Ricci, F, Corbelli, A, Affatato, R, Chilà, R, Chiappa, M, Brunelli, L, Fruscio, R, Pastorelli, R, Fiordaliso, F, Damia, G, Ricci, Francesca, Corbelli, Alessandro, Affatato, Roberta, Chilà, Rosaria, Chiappa, Michela, Brunelli, Laura, Fruscio, Robert, Pastorelli, Roberta, Fiordaliso, Fabio, and Damia, Giovanna
- Abstract
Mitochondria have attracted attention in cancer research as organelles associated with tumor development and response to therapy. We recently reported acquisition of resistance to cisplatin (DDP) associated with a metabolic rewiring in ovarian cancer patient-derived xenografts (PDXs) models. DDP-resistant PDXs models were obtained mimicking the clinical setting, treating mice bearing sensitive-DDP tumors with multiple cycles of DDP until the development of resistance. To further characterize the metabolic rewiring, the present study focused on tumor mitochondria. We analysed by transmission electron microscopy the mitochondria structure in two models of DDP-resistant and the corresponding DDP-sensitive PDXs and evaluated tumor mDNA content, the expression of genes and proteins involved in mitochondria functionality, and mitochondria fitness-related processes, such as autophagy. We observed a decrease in the number of mitochondria paralleled by an increased volume in DDP-resistant versus DDP-sensitive PDXs. DDP-resistant PDXs presented a higher percentage of damaged mitochondria, in particular of type 2 (concave-shape), and type 3 (cristolysis) damage. We found no difference in the mDNA content, and the expression of genes involved in mitochondrial biogenesis was similar between the sensitive and resistant PDXs. An upregulation of some genes involved in mitochondrial fitness in DDP-R versus DDP-S PDXs was observed. At protein level, no difference in the expression of proteins involved in mitochondrial function and biogenesis, and in autophagy/mitophagy was found. We here reported that the acquisition of DDP resistance is associated with morphological alterations in mitochondria, even if we couldn't find any dysregulation in the studied genes/proteins that could explain the observed differences.
- Published
- 2021
5. Regression of diabetic complications by islet transplantation in the rat
- Author
-
Remuzzi, A., Cornolti, R., Bianchi, R., Figliuzzi, M., Porretta-Serapiglia, C., Oggioni, N., Carozzi, V., Crippa, L., Avezza, F., Fiordaliso, F., Salio, M., Lauria, G., Lombardi, R., and Cavaletti, G.
- Published
- 2009
- Full Text
- View/download PDF
6. Development and spread of tau pathology after TBI
- Author
-
Zanier, E., primary, Bertani, I., additional, Vegliante, G., additional, Sammali, E., additional, Menon, D.K., additional, Fiordaliso, F., additional, Diomede, L., additional, Stocchetti, N., additional, Stewart, W., additional, and Chiesa, R., additional
- Published
- 2019
- Full Text
- View/download PDF
7. Evolution of Nanoparticle Protein Corona across the Blood-Brain Barrier
- Author
-
Cox, A, Andreozzi, P, Dal Magro, R, Fiordaliso, F, Corbelli, A, Talamini, L, Chinello, C, Raimondo, F, Magni, F, Tringali, M, Krol, S, Jacob Silva, P, Stellacci, F, Masserini, M, Re, F, COX, ALYSIA SARAH-MARIE, Andreozzi, Patrizia, Dal Magro, Roberta, Fiordaliso, Fabio, Corbelli, Alessandro, Talamini, Laura, Chinello, Clizia, Raimondo, Francesca, Magni, Fulvio, Tringali, Maria, Krol, Silke, Jacob Silva, Paulo, Stellacci, Francesco, Masserini, Massimo, Re, Francesca, Cox, A, Andreozzi, P, Dal Magro, R, Fiordaliso, F, Corbelli, A, Talamini, L, Chinello, C, Raimondo, F, Magni, F, Tringali, M, Krol, S, Jacob Silva, P, Stellacci, F, Masserini, M, Re, F, COX, ALYSIA SARAH-MARIE, Andreozzi, Patrizia, Dal Magro, Roberta, Fiordaliso, Fabio, Corbelli, Alessandro, Talamini, Laura, Chinello, Clizia, Raimondo, Francesca, Magni, Fulvio, Tringali, Maria, Krol, Silke, Jacob Silva, Paulo, Stellacci, Francesco, Masserini, Massimo, and Re, Francesca
- Abstract
Engineered nanoparticles offer the chance to improve drug transport and delivery through biological barriers, exploiting the possibility to leave the blood circulation and traverse the endothelial vascular bed, blood-brain barrier (BBB) included, to reach their target. It is known that nanoparticles gather molecules on their surface upon contact with biological fluids, forming the "protein corona", which can affect their fate and therapeutic/diagnostic performance, yet no information on the corona's evolution across the barrier has been gathered so far. Using a cellular model of the BBB and gold nanoparticles, we show that the composition of the corona undergoes dramatic quantitative and qualitative molecular modifications during passage from the "blood" to the "brain" side, while it is stable once beyond the BBB. Thus, we demonstrate that the nanoparticle corona dynamically and drastically evolves upon crossing the BBB and that its initial composition is not predictive of nanoparticle fate and performance once beyond the barrier at the target organ.
- Published
- 2018
8. A nanomedicine-based therapeutic approach restores memory and ameliorates amyloid pathology in Alzheimer's mouse models
- Author
-
Balducci, C, MANCINI, SIMONA, MINNITI, STEFANIA, La Vitola, P, Zotti, M, SANCINI, GIULIO ALFREDO, MAURI, MARIO, Cagnotto, A, Colombo, L, Fiordaliso, F, Grigoli, E, Salmona, M, Snellman, A, Haaparanta Solin, M, Forloni, G, MASSERINI, MASSIMO ERNESTO, RE, FRANCESCA, Balducci, C, Mancini, S, Minniti, S, La Vitola, P, Zotti, M, Sancini, G, Mauri, M, Cagnotto, A, Colombo, L, Fiordaliso, F, Grigoli, E, Salmona, M, Snellman, A, Haaparanta Solin, M, Forloni, G, Masserini, M, and Re, F
- Subjects
liposome ,Alzheimer ,Abeta ,oligomers ,nanomedicine ,cognitive impairment - Abstract
Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by deposition of the β-amyloid (Ab) peptide in the brain. Although many Ab-centric therapies have been attempted, they all failed and no efficacious therapy is available yet. Objectives. Main objectives of this study were to investigate the efficacy of multifunctional liposomes (Lip), designed to target the brain, to 1. promote disaggregation of brain Ab assemblies in AD mouse brain, 2. reduce brain Ab burden and 3. restore mouse memory, at a post-symptomatic stage. 4. Arrest pathology progression at a presymptomatic stage. Methods. Functionalized Lip with a peptide derived from apolipoprotein-E receptorbinding domain (mApoE) for blood-brain barrier targeting, and with phosphatidic acid (PA) for Ab binding (mApoE-PA-Lip) were administered (I.P.) for 3 weeks in post- and 4 months in pre-symptomatic APP/PS1 mice subsequently tested in the novel object recognition memory test (NORT). At the end mouse brains were collected and analyzed through histology and biochemistry for Ab deposition. Results. Administration of mApoE-PA-Lip decreased total insoluble brain Ab1-42, total plaque area and Ab oligomers. Plaque reduction was confirmed by PET imaging with [11C]-PIB. The reduction of brain Ab was associated with its increase in liver and spleen. Treatment also restored mouse impaired memory to normal at post-symptomatic ages and prevented its loss when administered at pre-symptomatic ages. Conclusions. These data suggest that bi-functionalized Lip destabilize brain Ab aggregates and promote peptide removal from the brain and its peripheral clearance. This innovative therapeutic approach can be considered as a new candidate for AD treatment.
- Published
- 2015
9. EFFECTS OF EXERCISE TRAINING ON ENDOTHELIAL PROGENITOR CELLS IN PATIENTS WITH CHRONIC HEART FAILURE
- Author
-
Sarto, P, Balducci, E, Balconi, G, Fiordaliso, F, Merlo, L, Tuzzato, G, Pappagallo, Gl, Frigato, N, Zanocco, A, Forestieri, C, Azzarello, G, Mazzucco, A, Valenti, Maria Teresa, Alborino, F, Noventa, D, Vinante, O, Pascotto, P, Sartore, S, Dejana, E, and Latini, R.
- Subjects
cardiac ,endothelial progenitor cells - Published
- 2007
10. Regression of diabetic complications by islet transplantation in the rat
- Author
-
Remuzzi, A, Cornolti, R, Bianchi, R, Figliuzzi, M, Porretta Serapiglia, C, Oggioni, N, Carozzi, V, Crippa, L, Avezza, F, Fiordaliso, F, Salio, M, Lauria, G, Lombardi, R, Cavaletti, G, OGGIONI, NORBERTO, CAROZZI, VALENTINA ALDA, AVEZZA, FEDERICA, CAVALETTI, GUIDO ANGELO, Remuzzi, A, Cornolti, R, Bianchi, R, Figliuzzi, M, Porretta Serapiglia, C, Oggioni, N, Carozzi, V, Crippa, L, Avezza, F, Fiordaliso, F, Salio, M, Lauria, G, Lombardi, R, Cavaletti, G, OGGIONI, NORBERTO, CAROZZI, VALENTINA ALDA, AVEZZA, FEDERICA, and CAVALETTI, GUIDO ANGELO
- Abstract
Type 1 diabetes is a chronic disease leading to complications such as peripheral neuropathies, nephropathy and cardiovascular disease. Pancreatic islet transplantation is being extensively investigated for blood glucose control in animals and in human type 1 diabetic patients, but the question of whether it can reverse long-term diabetic complications has not been fully explored. We investigated the effects of islet transplantation on diabetic complications in a rat model of streptozotocin-induced diabetes
- Published
- 2009
11. Myocyte apoptosis affects differently the male and female human heart in end-stage cardiac failure
- Author
-
Guerra, S, Kajstura, J, Wang, Xw, Fiordaliso, F, Finato, Nicoletta, DI LORETO, Carla, Beltrami, Carlo Alberto, and Anversa, P.
- Published
- 1998
12. Junctional adhesion molecule-A-deficient polyrnorphonuclear cells show reduced diapedesis in peritonitis and heart ischemia-reperfusion injury
- Author
-
Corada, M, Chimenti, S, Cera, M, Vinci, M, Salio, M, Fiordaliso, F, De Angelis, N, Villa, A, Bossi, M, Staszewsky, L, Vecchi, A, Parazzoli, D, Motoike, T, Latini, R, Dejana, E, Cera, MR, Staszewsky, LI, Dejana, E., VILLA, ANTONELLO, BOSSI, MARIO, Corada, M, Chimenti, S, Cera, M, Vinci, M, Salio, M, Fiordaliso, F, De Angelis, N, Villa, A, Bossi, M, Staszewsky, L, Vecchi, A, Parazzoli, D, Motoike, T, Latini, R, Dejana, E, Cera, MR, Staszewsky, LI, Dejana, E., VILLA, ANTONELLO, and BOSSI, MARIO
- Abstract
Junctional Adhesion Molecule-A (JAM-A) is a transmembrane adhesive protein expressed at endothelial junctions and in leukocytes. Here we report that JAM-A is required for the correct infiltration of polymorphonuclear leukocytes (PMN) into an inflamed peritoneum or in the heart upon ischemia-reperfusion injury. The defect was not observed in mice with an endothelium-restricted deficiency of the protein but was still detectable in mice transplanted with bone marrow from JAM-A(-/-) donors. Microscopic examination of mesenteric and heart microvasculature of JAM-A(-/-) mice showed high numbers of PMN adherent on the endothelium or entrapped between endothelial cells and the basement membrane. In vitro, in the absence of JAM-A, PMN adhered more efficiently to endothelial cells and basement membrane proteins, and their polarized movement was strongly reduced. This paper describes a nonredundant role of JAM-A in controlling PMN diapedesis through the vessel wall
- Published
- 2005
13. Eplerenone, a selective Aldosterone Blocker, improves diastolic Function in aged Rats with small-to-moderate myocardial Infarction
- Author
-
Masson, S, Staszewsky, L, Annoni, G, Carlo, E, Arosio, B, Bai, A, Calabresi, C, Martinoli, E, Salio, M, Fiordaliso, F, Scanziani, E, Rudolph, A, Latini, R, Rudolph, AE, Latini, R., ANNONI, GIORGIO, Masson, S, Staszewsky, L, Annoni, G, Carlo, E, Arosio, B, Bai, A, Calabresi, C, Martinoli, E, Salio, M, Fiordaliso, F, Scanziani, E, Rudolph, A, Latini, R, Rudolph, AE, Latini, R., and ANNONI, GIORGIO
- Abstract
Background: The incidence of cardiovascular diseases increases rapidly with age, and the elderly suffer higher morbidity and mortality. Aldosterone blockers have shown. benefits in patients with left ventricular (LV) dysfunction and heart failure after myocardial infarction (MI). However, aldosterone blockade efficacy has not been explored in aged animals with MI. Methods and Results: Small-to-moderate MI was induced by coronary artery ligation in 16-month old rats, divided into 3 groups: sham-operated (control, n = 9), MI (n. = 9), and MI fed a diet containing eplerenone (120 mg/kg/day, MI+Eplerenone, n = 9). given 18 days postsurgery and up to sacrifice 3 months later. At. sacrifice, untreated MI rats did not show overt systolic dysfunctiom but they had (1) echocardiographic evidences of impaired relaxation (increase of E wave deceleration time and of isovolumic relaxation time, decrease of peak E wave velocity), (2) hemodynamically impaired LV relaxation (LV -dP/dt from 7413 +/- 720 to 4956 +/- 475 mm Hg/s, P < .05), and (3) significant increase of collagen content in LV interstitium (from 4.27 +/- 0.23 to 5.34 +/- 0.24%, P < .01), and in aorta. (from 19 +/- 1 to 24 +/- 2%, P < .05). Eplerenone normalized echocardiographic and hemodynamic evidences of diastolic dysfunction, as well as myocardial. interstitial collagen and aortic fibrosis. (all parameters statistically different from untreated MI). Conclusion: In aged rats with small to moderate MI, eplerenone normalized diastolic relaxation, possibly through a reduction of interstitial fibrosis.
- Published
- 2004
14. 1002-84 Eplerenone normalizes diastolic relaxation and extracellular matrix accumulation in aged rats with myocardial infarction
- Author
-
Masson, S, Staszewsky, L, Annoni, G, Carlo, E, Arosio, B, Salio, M, Calabresi, C, Fiordaliso, F, Martinoli, E, Bai, A, Rudolph, A, Latini, R, Latini, R., ANNONI, GIORGIO, Masson, S, Staszewsky, L, Annoni, G, Carlo, E, Arosio, B, Salio, M, Calabresi, C, Fiordaliso, F, Martinoli, E, Bai, A, Rudolph, A, Latini, R, Latini, R., and ANNONI, GIORGIO
- Published
- 2004
15. Sunday, 18 July 2010
- Author
-
Schuchardt, M., primary, Toelle, M., additional, Huang, T., additional, Wiedon, A., additional, Van Der Giet, M., additional, Mill, C., additional, George, S., additional, Jeremy, J., additional, Santulli, G., additional, Illario, M., additional, Cipolletta, E., additional, Sorriento, D., additional, Del Giudice, C., additional, Anastasio, A., additional, Trimarco, B., additional, Iaccarino, G., additional, Jobs, A., additional, Wagner, C., additional, Kurtz, A., additional, De Wit, C., additional, Koller, A., additional, Suvorava, T., additional, Weber, M., additional, Dao, V., additional, Kojda, G., additional, Tsaousi, A., additional, Lyon, C., additional, Williams, H., additional, Barth, N., additional, Loot, A., additional, Fleming, I., additional, Keul, P., additional, Lucke, S., additional, Graeler, M., additional, Heusch, G., additional, Levkau, B., additional, Biessen, E., additional, De Jager, S., additional, Bermudez-Pulgarin, B., additional, Bot, I., additional, Abia, R., additional, Van Berkel, T., additional, Renger, A., additional, Noack, C., additional, Zafiriou, M., additional, Dietz, R., additional, Bergmann, M., additional, Zelarayan, L., additional, Hammond, J., additional, Hamelet, J., additional, Van Assche, T., additional, Belge, C., additional, Vanderper, A., additional, Langin, D., additional, Herijgers, P., additional, Balligand, J., additional, Perrot, A., additional, Neubert, M., additional, Posch, M., additional, Oezcelik, C., additional, Waldmuller, S., additional, Berger, F., additional, Scheffold, T., additional, Bouvagnet, P., additional, Ozcelik, C., additional, Lebreiro, A., additional, Martins, E., additional, Lourenco, P., additional, Cruz, C., additional, Martins, M., additional, Bettencourt, P., additional, Maciel, M., additional, Abreu-Lima, C., additional, Pilichou, K., additional, Bauce, B., additional, Rampazzo, A., additional, Carturan, E., additional, Corrado, D., additional, Thiene, G., additional, Basso, C., additional, Piccini, I., additional, Fortmueller, L., additional, Kuhlmann, M., additional, Schaefers, M., additional, Carmeliet, P., additional, Kirchhof, P., additional, Fabritz, L., additional, Sanchez, J., additional, Rodriguez-Sinovas, A., additional, Agullo, E., additional, Garcia-Dorado, D., additional, Lymperopoulos, A., additional, Rengo, G., additional, Gao, E., additional, Zincarelli, C., additional, Koch, W., additional, Morgan, P., additional, Diez, A., additional, Perez, N., additional, Cingolani, H., additional, Zahradnikova, A., additional, Polakova, E., additional, Zahradnik, I., additional, Fluschnik, N., additional, Sossalla, S., additional, Ort, K., additional, Neef, S., additional, Hasenfuss, G., additional, Maier, L., additional, Weinert, S., additional, Poitz, D., additional, Herold, J., additional, Schmeisser, A., additional, Strasser, J., additional, Braun-Dullaeus, R., additional, Nazari-Jahantigh, M., additional, Weber, C., additional, Schober, A., additional, Leuner, A., additional, Eichhorn, B., additional, Ravens, U., additional, Morawietz, H., additional, Babes, E., additional, Babes, V., additional, Popescu, M., additional, Ardelean, A., additional, Rus, M., additional, Bustea, C., additional, Gwozdz, P., additional, Csanyi, G., additional, Luzak, B., additional, Gajda, M., additional, Mateuszuk, L., additional, Chmura-Skirlinska, A., additional, Watala, C., additional, Chlopicki, S., additional, Kierzkowska, I., additional, Sulicka, J., additional, Kwater, A., additional, Strach, M., additional, Surdacki, A., additional, Siedlar, M., additional, Grodzicki, T., additional, Olieslagers, S., additional, Pardali, L., additional, Tchaikovski, V., additional, Ten Dijke, P., additional, Waltenberger, J., additional, Renner, M., additional, Redwan, B., additional, Winter, M., additional, Panzenboeck, A., additional, Jakowitsch, J., additional, Sadushi-Kolici, R., additional, Bonderman, D., additional, Lang, I., additional, Toso, A., additional, Tanini, L., additional, Pizzetti, T., additional, Leoncini, M., additional, Maioli, M., additional, Tedeschi, D., additional, Oliviero, C., additional, Bellandi, F., additional, Casprini, P., additional, Amato, M., additional, Molins, B., additional, Pena, E., additional, Badimon, L., additional, Ferreiro Gutierrez, J., additional, Ueno, M., additional, Alissa, R., additional, Dharmashankar, K., additional, Capodanno, D., additional, Desai, B., additional, Bass, T., additional, Angiolillo, D., additional, Chabielska, E., additional, Gromotowicz, A., additional, Szemraj, J., additional, Stankiewicz, A., additional, Zakrzeska, A., additional, Mohammed, S., additional, Molla, F., additional, Soldo, A., additional, Russo, I., additional, Germano, G., additional, Balconi, G., additional, Staszewsky, L., additional, Latini, R., additional, Lynch, F., additional, Austin, C., additional, Prendergast, B., additional, Keenan, D., additional, Malik, R., additional, Izzard, A., additional, Heagerty, A., additional, Czikora, A., additional, Lizanecz, E., additional, Rutkai, I., additional, Boczan, J., additional, Porszasz, R., additional, Papp, Z., additional, Edes, I., additional, Toth, A., additional, Colantuoni, A., additional, Vagnani, S., additional, Lapi, D., additional, Maroz-Vadalazhskaya, N., additional, Koslov, I., additional, Shumavetz, V., additional, Glibovskaya, T., additional, Ostrovskiy, Y., additional, Koutsiaris, A., additional, Tachmitzi, S., additional, Kotoula, M., additional, Giannoukas, A., additional, Tsironi, E., additional, Darago, A., additional, Orosz, P., additional, Megyesi, Z., additional, Schudeja, S., additional, Matschke, K., additional, Deussen, A., additional, Castro, M., additional, Cena, J., additional, Walsh, M., additional, Schulz, R., additional, Poddar, K., additional, Rha, S., additional, Ramasamy, S., additional, Park, J., additional, Choi, C., additional, Seo, H., additional, Park, C., additional, Oh, D., additional, Almeida, J., additional, Pimenta, S., additional, Bernardes, J., additional, Machado, J., additional, Sabatasso, S., additional, Laissue, J., additional, Hlushchuk, R., additional, Brauer-Krisch, E., additional, Bravin, A., additional, Blattmann, H., additional, Michaud, K., additional, Djonov, V., additional, Hirschberg, K., additional, Tarcea, V., additional, Pali, S., additional, Korkmaz, S., additional, Loganathan, S., additional, Merkely, B., additional, Karck, M., additional, Szabo, G., additional, Pagliani, L., additional, Faggin, E., additional, Rattazzi, M., additional, Puato, M., additional, Presta, M., additional, Grego, F., additional, Deriu, G., additional, Pauletto, P., additional, Kaiser, R., additional, Albrecht, K., additional, Schgoer, W., additional, Theurl, M., additional, Beer, A., additional, Wiedemann, D., additional, Steger, C., additional, Bonaros, N., additional, Kirchmair, R., additional, Kharlamov, A., additional, Cabaravdic, M., additional, Breuss, J., additional, Uhrin, P., additional, Binder, B., additional, Fiordaliso, F., additional, Maggioni, M., additional, Biondi, A., additional, Masson, S., additional, Cervo, L., additional, Francke, A., additional, Soenke, W., additional, Strasser, R., additional, Hecht, N., additional, Vajkoczy, P., additional, Woitzik, J., additional, Hackbusch, D., additional, Gatzke, N., additional, Duelsner, A., additional, Tsuprykov, O., additional, Slavic, S., additional, Buschmann, I., additional, Kappert, K., additional, Massaro, M., additional, Scoditti, E., additional, Carluccio, M., additional, Storelli, C., additional, Distante, A., additional, De Caterina, R., additional, Barandi, L., additional, Harmati, G., additional, Simko, J., additional, Horvath, B., additional, Szentandrassy, N., additional, Banyasz, T., additional, Magyar, J., additional, Nanasi, P., additional, Kaya, A., additional, Uzunhasan, I., additional, Yildiz, A., additional, Yigit, Z., additional, Turkoglu, C., additional, Doisne, N., additional, Zannad, N., additional, Hivert, B., additional, Cosnay, P., additional, Maupoil, V., additional, Findlay, I., additional, Virag, L., additional, Kristof, A., additional, Koncz, I., additional, Szel, T., additional, Jost, N., additional, Biliczki, P., additional, Papp, J., additional, Varro, A., additional, Bukowska, A., additional, Skopp, K., additional, Hammwoehner, M., additional, Huth, C., additional, Bode-Boeger, S., additional, Goette, A., additional, Workman, A., additional, Dempster, J., additional, Marshall, G., additional, Rankin, A., additional, Revnic, C., additional, Ginghina, C., additional, Revnic, F., additional, Yakushev, S., additional, Petrushanko, I., additional, Makhro, A., additional, Segato Komniski, M., additional, Mitkevich, V., additional, Makarov, A., additional, Gassmann, M., additional, Bogdanova, A., additional, Rutkovskiy, A., additional, Mariero, L., additional, Stenslokken, K., additional, Valen, G., additional, Vaage, J., additional, Dizayee, S., additional, Kaestner, S., additional, Kuck, F., additional, Piekorz, R., additional, Hein, P., additional, Matthes, J., additional, Nurnberg, B., additional, Herzig, S., additional, Hertel, F., additional, Switalski, A., additional, Bender, K., additional, Kienitz, M.-C., additional, Pott, L., additional, Fornai, L., additional, Angelini, A., additional, Erika Amstalden Van Hove, E., additional, Fedrigo, M., additional, Heeren, R., additional, Kruse, M., additional, Pongs, O., additional, Lehmann, H., additional, Martens-Lobenhoffer, J., additional, Roehl, F., additional, Radicke, S., additional, Cotella, C., additional, Sblattero, D., additional, Schaefer, M., additional, Wettwer, E., additional, Santoro, C., additional, Seyler, C., additional, Kulzer, M., additional, Zitron, E., additional, Scholz, E., additional, Welke, F., additional, Thomas, D., additional, Karle, C., additional, Schmidt, K., additional, Dobrev, D., additional, Houshmand, N., additional, Menesi, D., additional, Cotella, D., additional, Szuts, V., additional, Puskas, L., additional, Kiss, I., additional, Deak, F., additional, Tereshchenko, S., additional, Gladyshev, M., additional, Kalachova, G., additional, Syshchik, N., additional, Gogolashvili, N., additional, Dedok, E., additional, Evert, L., additional, Wenzel, J., additional, Brandenburger, M., additional, Bogdan, R., additional, Richardt, D., additional, Reppel, M., additional, Hescheler, J., additional, Dendorfer, A., additional, Terlau, H., additional, Wiegerinck, R., additional, Galvez-Monton, C., additional, Jorge, E., additional, Martinez, R., additional, Ricart, E., additional, Cinca, J., additional, Bagavananthem Andavan, G., additional, Lemmens Gruber, R., additional, Brack, K., additional, Coote, J., additional, Ng, G., additional, Daimi, H., additional, Haj Khelil, A., additional, Neji, A., additional, Ben Hamda, K., additional, Maaoui, S., additional, Aranega, A., additional, Chibani, J., additional, Franco Jaime, D., additional, Tanko, A.-S., additional, Daniel, J.-M., additional, Bielenberg, W., additional, Stieger, P., additional, Tillmanns, H., additional, Sedding, D., additional, Fortini, C., additional, Toffoletto, B., additional, Fucili, A., additional, Beltrami, A., additional, Fiorelli, V., additional, Francolini, G., additional, Ferrari, R., additional, Beltrami, C., additional, Castellani, C., additional, Ravara, B., additional, Tavano, R., additional, Vettor, R., additional, De Coppi, P., additional, Papini, E., additional, Gunetti, M., additional, Fagioli, F., additional, Suffredini, S., additional, Sartiani, L., additional, Stillitano, F., additional, Mugelli, A., additional, Cerbai, E., additional, Krausgrill, B., additional, Halbach, M., additional, Soemantri, S., additional, Schenk, K., additional, Lange, N., additional, Saric, T., additional, Muller-Ehmsen, J., additional, Kavanagh, D., additional, Zhao, Y., additional, Yemm, A., additional, Kalia, N., additional, Wright, E., additional, Farrell, K., additional, Wallrapp, C., additional, Geigle, P., additional, Lewis, A., additional, Stratford, P., additional, Malik, N., additional, Holt, C., additional, Raths, M., additional, Zagallo, M., additional, Luni, C., additional, Serena, E., additional, Cimetta, E., additional, Zatti, S., additional, Giobbe, G., additional, Elvassore, N., additional, Zaglia, T., additional, Zambon, A., additional, Gordon, K., additional, Mioulane, M., additional, Foldes, G., additional, Ali, N., additional, Harding, S., additional, Gorbe, A., additional, Szunyog, A., additional, Varga, Z., additional, Pirity, M., additional, Rungaruniert, S., additional, Dinnyes, A., additional, Csont, T., additional, Ferdinandy, P., additional, Iqbal, A., additional, Schneider, M. D., additional, Khodjaeva, E., additional, Ibadov, R., additional, Khalikulov, K., additional, Mansurov, A., additional, Astvatsatryan, A., additional, Senan, M., additional, Nemeth, A., additional, Lenkey, Z., additional, Ajtay, Z., additional, Cziraki, A., additional, Sulyok, E., additional, Horvath, I., additional, Lobenhoffer, J., additional, Bode-Boger, S., additional, Li, J., additional, He, Y., additional, Yang, X., additional, Wang, F., additional, Xu, H., additional, Li, X., additional, Zhao, X., additional, Lin, Y., additional, Juszynski, M., additional, Ciszek, B., additional, Jablonska, A., additional, Stachurska, E., additional, Ratajska, A., additional, Atkinson, A., additional, Inada, S., additional, Sleiman, R., additional, Zhang, H., additional, Boyett, M., additional, Dobrzynski, H., additional, Fedorenko, O., additional, Hao, G., additional, Yanni, J., additional, Buckley, D., additional, Anderson, R., additional, Ma, Y., additional, Ma, X., additional, Hu, Y., additional, Yang, Y., additional, Huang, D., additional, Liu, F., additional, Huang, Y., additional, Liu, C., additional, Jedrzejczyk, T., additional, Balwicki, L., additional, Wierucki, L., additional, Zdrojewski, T., additional, Agarkova, I., additional, Vogel, J., additional, Korybalska, K., additional, Pyda, M., additional, Witowski, J., additional, Ibatov, A., additional, Sozmen, N., additional, Seymen, A., additional, Tuncay, E., additional, Turan, B., additional, Chen, B., additional, Houston-Feenstra, L., additional, Chiong, J. R., additional, Jutzy, K., additional, Furundzija, V., additional, Kaufmann, J., additional, Meyborg, H., additional, Fleck, E., additional, Stawowy, P., additional, Ksiezycka-Majczynska, E., additional, Lubiszewska, B., additional, Kruk, M., additional, Kurjata, P., additional, Ruzyllo, W., additional, Driesen, R., additional, Coenen, T., additional, Fagard, R., additional, Sipido, K., additional, Petrov, V., additional, Aksentijevic, D., additional, Lygate, C., additional, Makinen, K., additional, Sebag-Montefiore, L., additional, Medway, D., additional, Schneider, J., additional, Neubauer, S., additional, Gasser, R., additional, Holzwart, E., additional, Rainer, P., additional, Von Lewinski, D., additional, Maechler, H., additional, Gasser, S., additional, Roessl, U., additional, Pieske, B., additional, Krueger, J., additional, Kintscher, U., additional, Podramagi, T., additional, Paju, K., additional, Piirsoo, A., additional, Roosimaa, M., additional, Kadaja, L., additional, Orlova, E., additional, Ruusalepp, A., additional, Seppet, E., additional, Auquier, J., additional, Ginion, A., additional, Hue, L., additional, Horman, S., additional, Beauloye, C., additional, Vanoverschelde, J., additional, Bertrand, L., additional, Fekete, V., additional, Zvara, A., additional, Pipis, J., additional, Konya, C., additional, Csonka, C., additional, Kraigher-Krainer, E., additional, Von Lewinksi, D., additional, Gonzalez-Loyola, A., additional, Barba, I., additional, Fernandez-Sanz, C., additional, Ruiz-Meana, M., additional, Forteza, M., additional, Bodi Peris, V., additional, Monleon, D., additional, Mainar, L., additional, Morales, J., additional, Moratal, D., additional, Trapero, I., additional, Chorro, F., additional, Leszek, P., additional, Sochanowicz, B., additional, Szperl, M., additional, Kolsut, P., additional, Piotrowski, W., additional, Rywik, T., additional, Danko, B., additional, Kruszewski, M., additional, Stanley, W., additional, Khairallah, R., additional, Khanna, N., additional, O'shea, K., additional, Kristian, T., additional, Hecker, P., additional, Des Rosiers, R., additional, Fiskum, G., additional, Fernandez-Alfonso, M., additional, Guzman-Ruiz, R., additional, Somoza, B., additional, Gil-Ortega, M., additional, Attane, C., additional, Castan-Laurell, I., additional, Valet, P., additional, Ruiz-Gayo, M., additional, Denissevich, T., additional, Schrepper, A., additional, Schwarzer, M., additional, Amorim, P., additional, Schoepe, M., additional, Mohr, F., additional, Doenst, T., additional, Chiellini, G., additional, Ghelardoni, S., additional, Saba, A., additional, Marchini, M., additional, Frascarelli, S., additional, Raffaelli, A., additional, Scanlan, T., additional, Zucchi, R., additional, Van Den Akker, N., additional, Molin, D., additional, Kolk, F., additional, Jeukens, F., additional, Olde Engberink, R., additional, Post, M., additional, Verbruggen, S., additional, Schulten, H., additional, Rochais, F., additional, Kelly, R., additional, Aberg, M., additional, Johnell, M., additional, Wickstrom, M., additional, Siegbahn, A., additional, Dimitrakis, P., additional, Groppalli, V., additional, Ott, D., additional, Seifriz, F., additional, Suter, T., additional, Zuppinger, C., additional, Kashcheyeu, Y., additional, Mueller, R., additional, Wiesen, M., additional, Gruendemann, D., additional, Falcao-Pires, I., additional, Fontes-Sousa, A., additional, Lopes-Conceicao, L., additional, Bras-Silva, C., additional, Leite-Moreira, A., additional, Bukauskas, F., additional, Palacios-Prado, N., additional, Norheim, F., additional, Raastad, T., additional, Thiede, B., additional, Drevon, C., additional, Haugen, F., additional, Lindner, D., additional, Westermann, D., additional, Zietsch, C., additional, Schultheiss, H.-P., additional, Tschoepe, C., additional, Horn, M., additional, Graham, H., additional, Hall, M., additional, Richards, M., additional, Clarke, J., additional, Dibb, K., additional, Trafford, A., additional, Cheng, C.-F., additional, Lin, H., additional, Eigeldiger-Berthou, S., additional, Buntschu, P., additional, Frobert, A., additional, Flueck, M., additional, Tevaearai, H., additional, Kadner, A., additional, Mikhailov, A., additional, Torrado, M., additional, Centeno, A., additional, Lopez, E., additional, Lourido, L., additional, Castro Beiras, A., additional, Popov, T., additional, Srdanovic, I., additional, Petrovic, M., additional, Canji, T., additional, Kovacevic, M., additional, Jovelic, A., additional, Sladojevic, M., additional, Panic, G., additional, Kararigas, G., additional, Fliegner, D., additional, Regitz-Zagrosek, V., additional, De La Rosa Sanchez, A., additional, Dominguez, J., additional, Sedmera, D., additional, Franco, D., additional, Medunjanin, S., additional, Burgbacher, F., additional, Han, W., additional, Zhang, J., additional, Gao, X., additional, Bayliss, C., additional, Song, W., additional, Stuckey, D., additional, Dyer, E., additional, Leung, M.-C., additional, Monserrat, L., additional, Marston, S., additional, Fusco, A., additional, Paillard, M., additional, Liang, J., additional, Strub, G., additional, Gomez, L., additional, Hait, N., additional, Allegood, J., additional, Lesnefsky, E., additional, Spiegel, S., additional, Zuchi, C., additional, Coiro, S., additional, Bettini, M., additional, Ciliberti, G., additional, Mancini, I., additional, Tritto, I., additional, Becker, L., additional, Ambrosio, G., additional, Adam, T., additional, Sharp, S., additional, Opie, L., additional, Lecour, S., additional, Khaliulin, I., additional, Parker, J., additional, Halestrap, A., additional, Kandasamy, A., additional, Osterholt, M., additional, Miro-Casas, E., additional, Boengler, K., additional, Menazza, S., additional, Canton, M., additional, Sheeran, F., additional, Di Lisa, F., additional, Pepe, S., additional, Borchi, E., additional, Manni, M., additional, Bargelli, V., additional, Giordano, C., additional, D'amati, G., additional, Nediani, C., additional, Raimondi, L., additional, Micova, P., additional, Balkova, P., additional, Kolar, F., additional, Neckar, J., additional, Novak, F., additional, Novakova, O., additional, Schuchardt, M., additional, Pruefer, N., additional, Pruefer, J., additional, Jankowski, V., additional, Jankowski, J., additional, Su, Y., additional, Zervou, S., additional, Seidel, B., additional, Radovits, T., additional, Barnucz, E., additional, Aggeli, I., additional, Kefaloyianni, E., additional, Beis, I., additional, Gaitanaki, C., additional, Lacerda, L., additional, Somers, S., additional, Paur, H., additional, Nikolaev, V., additional, Lyon, A., additional, Silva, S., additional, Gomes, M., additional, Ferreira, P., additional, Capuano, V., additional, Ferron, L., additional, Ruchon, Y., additional, Ben Mohamed, F., additional, Renaud, J.-F., additional, Goncalves, N., additional, Gavina, C., additional, Pinho, S., additional, Moura, C., additional, Amorim, M., additional, Pinho, P., additional, Christ, T., additional, Molenaar, P., additional, Kaumann, A., additional, Kletsiou, E., additional, Giannakopoulou, M., additional, Bozas, E., additional, Iliodromitis, E., additional, Anastasiou-Nana, M., additional, Papathanassoglou, E., additional, Chottova Dvorakova, M., additional, Mistrova, E., additional, Slavikova, J., additional, Hynie, S., additional, Sida, P., additional, Klenerova, V., additional, Zakrzewicz, A., additional, Hoffmann, C., additional, Hohberg, M., additional, Chlench, S., additional, Maroski, J., additional, Drab, M., additional, Siegel, G., additional, Pries, A., additional, Schrot, G., additional, Wilck, N., additional, Fechner, M., additional, Arias, A., additional, Meiners, S., additional, Baumann, G., additional, Stangl, V., additional, Stangl, K., additional, Ludwig, A., additional, Christ, A., additional, Eijgelaar, W., additional, Daemen, M., additional, Penfold, M., additional, Schall, T., additional, Hintenberger, R., additional, Kaun, C., additional, Pfaffenberger, S., additional, Maurer, G., additional, Huber, K., additional, Wojta, J., additional, Demyanets, S., additional, Titov, V., additional, Chin-Dusting, J., additional, Vaisman, B., additional, Khong, S., additional, Remaley, A., additional, Andrews, K., additional, Hoeper, A., additional, Khalid, A., additional, Fuglested, B., additional, Aasum, E., additional, Larsen, T., additional, Diebold, I., additional, Petry, A., additional, Djordjevic, T., additional, Belaiba, R., additional, Fratz, S., additional, Hess, J., additional, Kietzmann, T., additional, Goerlach, A., additional, Chess, D., additional, Walsh, K., additional, Van Der Velden, J., additional, Moreira-Goncalves, D., additional, Paulus, W., additional, Niessen, H., additional, Perlini, S., additional, Azibani, F., additional, Tournoux, F., additional, Fazal, L., additional, Polidano, E., additional, Merval, R., additional, Chatziantoniou, C., additional, Samuel, J., additional, Delcayre, C., additional, Mgandela, P., additional, Brooksbank, R., additional, Maswanganyi, T., additional, Woodiwiss, A., additional, Norton, G., additional, Makaula, S., additional, Bucciantini, M., additional, Spinelli, V., additional, Coppini, R., additional, Russo, E., additional, Stefani, M., additional, Sukumaran, V., additional, Watanabe, K., additional, Ma, M., additional, Thandavarayan, R., additional, Azrozal, W., additional, Sari, F., additional, Shimazaki, H., additional, Kobayashi, Y., additional, Roleder, T., additional, Golba, K., additional, Deja, M., additional, Malinowski, M., additional, Wos, S., additional, Grebe, M., additional, Preissner, K., additional, Ercan, E., additional, Guven, A., additional, Asgun, F., additional, Ickin, M., additional, Ercan, F., additional, Kaplan, A., additional, Yavuz, O., additional, Bagla, S., additional, Kuka, J., additional, Vilskersts, R., additional, Vavers, E., additional, Liepins, E., additional, Dambrova, M., additional, Duerr, G., additional, Suchan, G., additional, Heuft, T., additional, Klaas, T., additional, Zimmer, A., additional, Welz, A., additional, Fleischmann, B., additional, Dewald, O., additional, Voelkl, J., additional, Haubner, B., additional, Kremser, C., additional, Mayr, A., additional, Klug, G., additional, Reiner, M., additional, Pachinger, O., additional, Metzler, B., additional, Pisarenko, O., additional, Shulzhenko, V., additional, Pelogeykina, Y., additional, Khatri, D., additional, Studneva, I., additional, Bencsik, P., additional, Kocsis, G., additional, Shamloo, M., additional, Woodburn, K., additional, Szucs, G., additional, Kupai, K., additional, Csont, C., additional, Kocsisne Fodor, G., additional, Monostori, P., additional, and Turi, S., additional
- Published
- 2010
- Full Text
- View/download PDF
16. Left ventricular Response to beta-adrenergic Stimulation in aging Rats
- Author
-
Masson, S, Arosio, B, Fiordaliso, F, Gagliano, N, Calvillo, L, Santambrogio, D, D'Aquila, S, Vergani, C, Latini, R, Annoni, G, ANNONI, GIORGIO, Masson, S, Arosio, B, Fiordaliso, F, Gagliano, N, Calvillo, L, Santambrogio, D, D'Aquila, S, Vergani, C, Latini, R, Annoni, G, and ANNONI, GIORGIO
- Abstract
The incidence of heart failure in the population increases steeply among older people. Overactivation of the sympathetic nervous system is associated to and responsible for worsening of heart failure, This study describes the influence of aging on short-term left ventricular (LV) adaptation to b-adrenergic: stimulation in Wistar rats. In controls at 18 mo, interstitial fibrosis was increased with respect to 3-mo-old rats, whereas myocytes dimension and the messenger RNA (mRNA) abundance of atrial natriuretic peptide (ANP), a(2) (I) procollagen, transforming growth factor (TGFb(1), TGF-b(3)), and secreted protein, acidic and rich in cysteine (SPARC) were not different. To determine how aging affects LV adaptation to adrenergic stimulation, two groups of animals received isoproterenol (ISO, 1 mg/kg/d) for 3 days. There was no significant difference between young and older rats with respect to increase in LV weight, myocytes dimension, and mRNA abundance of all the genes considered, except a(1)(III) procollagen. These findings indicate that despite limited compensatory hypertrophy and higher fibrosis, LV from aged nonsenescent rats preserves the capacity to adapt to b-adrenergic stimulation through the upregulation of several genes encoding extracellular matrix-related proteins.
- Published
- 2000
17. Antioxidant treatment attenuates hyperglycemia-induced cardiomyocyte death in rats
- Author
-
FIORDALISO, F, primary, BIANCHI, R, additional, STASZEWSKY, L, additional, CUCCOVILLO, I, additional, DONI, M, additional, LARAGIONE, T, additional, SALIO, M, additional, SAVINO, C, additional, MELUCCI, S, additional, and SANTANGELO, F, additional
- Published
- 2004
- Full Text
- View/download PDF
18. CARDIOVASCULAR EFFECTS OF CHRONIC LOW-DOSE OUABAIN ADMINISTRATION IN RATS
- Author
-
Schiavone, A., primary, Palazzo, F., additional, Serra, F., additional, Fiordaliso, F., additional, Cuccovillo, I., additional, Bianchi, G., additional, Micheletti, R., additional, and Ferrari, P., additional
- Published
- 2004
- Full Text
- View/download PDF
19. Cognitive deficits associated with alteration of synaptic metaplasticity precede plaque deposition in AβPP23 transgenic mice.
- Author
-
Balducci C, Tonini R, Zianni E, Nazzaro C, Fiordaliso F, Salio M, Vismara L, Gardoni F, Di Luca M, Carli M, Forloni G, Balducci, Claudia, Tonini, Raffaella, Zianni, Elisa, Nazzaro, Cristiano, Fiordaliso, Fabio, Salio, Monica, Vismara, Lorenzo, Gardoni, Fabrizio, and Di Luca, Monica
- Abstract
Synaptic dysfunction is an early event in the development of Alzheimer's disease (AD) and relates closely to the cognitive impairment characterizing this neurodegenerative process. A causative association has been proposed, largely on the basis of in vitro studies, between memory decline, soluble amyloid-β (Aβ) oligomers and alterations of glutamatergic neurotransmission. We aimed here to characterize in vivo N-methyl-D-aspartate receptor (NMDAR)-mediated signaling, at an early stage of AD, before extracellular amyloid plaques are deposited. We assessed the functional link between cognitive abilities and NMDAR-mediated pharmacological responses of six-month-old AβPP23 transgenic mice (AβPP23tg), overexpressing the human amyloid-β protein precursor carrying the Swedish double mutation. We found evidence of cognitive impairments in these mice, indicated by deficits in the delayed-non-matching-to-place task. Alterations of NMDAR-mediated signaling in this mouse model were confirmed by the reduced sensitivity of motor-activation and working memory to pharmacological inhibition of NMDAR activity. At the molecular level, AβPP23tg mice show hippocampal alterations in the trafficking of synaptic NMDAR subunits NR2A and NR2B and at an ultrastructural analysis show Aβ oligomers intracellularly localized in the synaptic compartments. Importantly, the behavioral and biochemical alterations of NMDAR signaling are associated with the inhibition of long-term synaptic potentiation and inversion of metaplasticity at CA1 synapses in hippocampal slices from AβPP23tg mice. These results indicate a general impairment of synaptic function and learning and memory in young AβPP23tg mice with Aβ oligomers but no amyloid plaques. [ABSTRACT FROM AUTHOR]
- Published
- 2010
20. Do non-hemopoietic effects of erythropoietin play a beneficial role in heart failure?
- Author
-
Latini R, Brines M, Fiordaliso F, Latini, Roberto, Brines, Michael, and Fiordaliso, Fabio
- Abstract
Erythropoietin (EPO) is not solely a hormone charged with regulating the proliferation and differentiation of erythroid cells. Indeed, EPO is synthesized locally by many cells, especially under conditions of stress or injury. In these paracrine/autocrine settings, EPO plays a crucial protective-restorative role, activating cytoprotection (e.g., in the brain, heart, and kidney), reducing inflammatory responses, preserving vascular integrity, and mobilizing stem cells, including proliferation and differentiation of endothelial progenitor cells. EPO administration prevents cardiac myocyte apoptosis and decreases infarct size in several studies using rodent models of myocardial infarction. Recently, some key steps of the signaling pathways by which EPO confers cardioprotection have been identified. The striking finding distilled from work by numerous independent investigators is that EPO mediates protection in the heart (as well as other tissues) by multiple pathways that are not redundant. The following actions proven to play a role in protection from acute cardiac injury can exert a beneficial effect in chronic heart failure (HF): (a) antiapoptotic effect, (b) mobilization of endothelial progenitor cells from bone marrow, and (c) anti-hypertrophic effects. The evidences discussed herein provide a strong basis for the ongoing clinical trials testing EPO in chronic HF. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
21. Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell death.
- Author
-
Fiordaliso, Fabio, Leri, Annarosa, Cesselli, Daniela, Limana, Federica, Safai, Bijan, Nadal-Ginard, Bernardo, Anversa, Piero, Kajstura, Jan, Fiordaliso, F, Leri, A, Cesselli, D, Limana, F, Safai, B, Nadal-Ginard, B, Anversa, P, and Kajstura, J
- Subjects
HYPERGLYCEMIA ,CELL death ,P53 antioncogene ,PHYSIOLOGY ,PROTEIN metabolism ,DNA metabolism ,ANIMAL experimentation ,APOPTOSIS ,CELL culture ,COMPARATIVE studies ,GENES ,GLYCOSYLATION ,HEART ventricles ,HYDROGEN-ion concentration ,RESEARCH methodology ,MEDICAL cooperation ,MYOCARDIUM ,PHOSPHORYLATION ,PROTEINS ,RATS ,RESEARCH ,TRANSFERASES ,ANGIOTENSIN II ,EVALUATION research ,LOSARTAN ,PHARMACODYNAMICS - Abstract
To determine whether enzymatic p53 glycosylation leads to angiotensin II formation followed by p53 phosphorylation, prolonged activation of the renin-angiotensin system, and apoptosis, ventricular myocytes were exposed to levels of glucose mimicking diabetic hyperglycemia. At a high glucose concentration, O-glycosylation of p53 occurred between 10 and 20 min, reached its peak at 1 h, and then decreased with time. Angiotensin II synthesis increased at 45 min and 1 h, resulting in p38 mitogen-activated protein (MAP) kinase-driven p53 phosphorylation at Ser 390. p53 phosphorylation was absent at the early time points, becoming evident at 1 h, and increasing progressively from 3 h to 4 days. Phosphorylated p53 at Ser 18 and activated c-Jun NH(2)-terminal kinases were identified with hyperglycemia, whereas extracellular signal-regulated kinase was not phosphorylated. Upregulation of p53 was associated with an accumulation of angiotensinogen and AT(1) and enhanced production of angiotensin II. Bax quantity also increased. These multiple adaptations paralleled the concentrations of glucose in the medium and the duration of the culture. Myocyte death by apoptosis directly correlated with glucose and angiotensin II levels. Inhibition of O-glycosylation prevented the initial synthesis of angiotensin II, p53, and p38-MAP kinase (MAPK) phosphorylation and apoptosis. AT(1) blockade had no influence on O-glycosylation of p53, but it interfered with p53 phosphorylation; losartan also prevented phosphorylation of p38-MAPK by angiotensin II. Inhibition of p38-MAPK mimicked at a more distal level the consequences of losartan. In conclusion, these in vitro results support the notion that hyperglycemia with diabetes promotes myocyte apoptosis mediated by activation of p53 and effector responses involving the local renin-angiotensin system. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
22. IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress.
- Author
-
Kajstura, Jan, Fiordaliso, Fabio, Andreoli, Anna Maria, Baosheng Li, Chimenti, Stefano, Medow, Marvin S., Limana, Federica, Nadal-Ginard, Bernardo, Leri, Annarosa, Anversa, Piers, Kajstura, J, Fiordaliso, F, Andreoli, A M, Li, B, Chimenti, S, Medow, M S, Limana, F, Nadal-Ginard, B, Leri, A, and Anversa, P
- Subjects
IMMUNOGLOBULINS ,CARDIOMYOPATHIES ,DIABETES ,ANGIOTENSINS - Abstract
Stimulation of the local renin-angiotensin system and apoptosis characterize the diabetic heart. Because IGF-1 reduces angiotensin (Ang) II and apoptosis, we tested whether streptozotocin-induced diabetic cardiomyopathy was attenuated in IGF-1 transgenic mice (TGM). Diabetes progressively depressed ventricular performance in wild-type mice (WTM) but had no hemodynamic effect on TGM. Myocyte apoptosis measured at 7 and 30 days after the onset of diabetes was twofold higher in WTM than in TGM. Myocyte necrosis was apparent only at 30 days and was more severe in WTM. Diabetic nontransgenic mice lost 24% of their ventricular myocytes and showed a 28% myocyte hypertrophy; both phenomena were prevented by IGF-1. In diabetic WTM, p53 was increased in myocytes, and this activation of p53 was characterized by upregulation of Bax, angiotensinogen, Ang type 1 (AT(1)) receptors, and Ang II. IGF-1 overexpression decreased these biochemical responses. In vivo accumulation of the reactive O(2) product nitrotyrosine and the in vitro formation of H(2)O(2)-(.)OH in myocytes were higher in diabetic WTM than TGM. Apoptosis in vitro was detected in myocytes exhibiting high H(2)O(2)-(.)OH fluorescence, and apoptosis in vivo was linked to the presence of nitrotyrosine. H(2)O(2)-(.)OH generation and myocyte apoptosis in vitro were inhibited by the AT(1) blocker losartan and the O(2) scavenger TIRON: In conclusion, IGF-1 interferes with the development of diabetic myopathy by attenuating p53 function and Ang II production and thus AT(1) activation. This latter event might be responsible for the decrease in oxidative stress and myocyte death by IGF-1. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
23. Left ventricular response to beta-adrenergic stimulation in aging rats.
- Author
-
Masson, Serge, Arosio, Beatrice, Masson, S, Arosio, B, Fiordaliso, F, Gagliano, N, Calvillo, L, Santambrogio, D, D'Aquila, S, Vergani, C, Latini, R, and Annoni, G
- Subjects
AGING ,LEFT heart ventricle ,BIOLOGICAL adaptation ,HEALTH - Abstract
The incidence of heart failure in the population increases steeply among older people. Overactivation of the sympathetic nervous system is associated to and responsible for worsening of heart failure. This study describes the influence of aging on short-term left ventricular (LV) adaptation to b-adrenergic stimulation in Wistar rats. In controls at 18 mo, interstitial fibrosis was increased with respect to 3-mo-old rats, whereas myocytes dimension and the messenger RNA (mRNA) abundance of atrial natriuretic peptide (ANP), a2(I) procollagen, transforming growth factor (TGF-b1, TGF-b3), and secreted protein, acidic and rich in cysteine (SPARC) were not different. To determine how aging affects LV adaptation to adrenergic stimulation, two groups of animals received isoproterenol (ISO, 1 mg/kg/d) for 3 days. There was no significant difference between young and older rats with respect to increase in LV weight, myocytes dimension, and mRNA abundance of all the genes considered, except a1(III) procollagen. These findings indicate that despite limited compensatory hypertrophy and higher fibrosis, LV from aged nonsenescent rats preserves the capacity to adapt to b-adrenergic stimulation through the upregulation of several genes encoding extracellular matrix-related proteins. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
24. Age-dependent expression of fibrosis-related genes and collagen deposition in the rat myocardium
- Author
-
Annoni, G., Luvara, G., Arosio, B., Gagliano, N., Fiordaliso, F., Santambrogio, D., Jeremic, G., Mircoli, L., Latini, R., and Vergani, C.
- Published
- 1998
- Full Text
- View/download PDF
25. Mitochondrial structural alterations in ovarian cancer patient-derived xenografts resistant to cisplatin
- Author
-
francesca ricci, Corbelli A, Roberta Affatato, Chilà R, Michela Chiappa, Brunelli L, Fruscio R, Pastorelli R, Fiordaliso F, Damia G, Ricci, F, Corbelli, A, Affatato, R, Chilà, R, Chiappa, M, Brunelli, L, Fruscio, R, Pastorelli, R, Fiordaliso, F, and Damia, G
- Subjects
endocrine system diseases ,Original Article ,platinum resistance and ovarian carcinoma ,microscopia elettronica, mitocondri, modelli xenograft derivati da pazienti con carcinoma ovarico ,Mitochondria - Abstract
Mitochondria have attracted attention in cancer research as organelles associated with tumor development and response to therapy. We recently reported acquisition of resistance to cisplatin (DDP) associated with a metabolic rewiring in ovarian cancer patient-derived xenografts (PDXs) models. DDP-resistant PDXs models were obtained mimicking the clinical setting, treating mice bearing sensitive-DDP tumors with multiple cycles of DDP until the development of resistance. To further characterize the metabolic rewiring, the present study focused on tumor mitochondria. We analysed by transmission electron microscopy the mitochondria structure in two models of DDP-resistant and the corresponding DDP-sensitive PDXs and evaluated tumor mDNA content, the expression of genes and proteins involved in mitochondria functionality, and mitochondria fitness-related processes, such as autophagy. We observed a decrease in the number of mitochondria paralleled by an increased volume in DDP-resistant versus DDP-sensitive PDXs. DDP-resistant PDXs presented a higher percentage of damaged mitochondria, in particular of type 2 (concave-shape), and type 3 (cristolysis) damage. We found no difference in the mDNA content, and the expression of genes involved in mitochondrial biogenesis was similar between the sensitive and resistant PDXs. An upregulation of some genes involved in mitochondrial fitness in DDP-R versus DDP-S PDXs was observed. At protein level, no difference in the expression of proteins involved in mitochondrial function and biogenesis, and in autophagy/mitophagy was found. We here reported that the acquisition of DDP resistance is associated with morphological alterations in mitochondria, even if we couldn’t find any dysregulation in the studied genes/proteins that could explain the observed differences.
26. The mesoangioblast, a multipotent embryonic cell from dorsal aorta, repairs the infarcted heart: comparative efficacy with bone marrow-derived stem cells and fibroblasts
- Author
-
Latini, R., Cossu, G., Dejana, E., Innocenzi, A., Cusella, G., Bai, A., Martinoli, E., Carlo, E., Fiordaliso, F., Zanetta, L., Staszewsky, L., Mavilio, F., and Balconi, G.
- Published
- 2004
- Full Text
- View/download PDF
27. PGC1α/β Expression Predicts Therapeutic Response to Oxidative Phosphorylation Inhibition in Ovarian Cancer
- Author
-
Carmen Ghilardi, Catarina Moreira-Barbosa, Laura Brunelli, Paola Ostano, Nicolò Panini, Monica Lupi, Alessia Anastasia, Fabio Fiordaliso, Monica Salio, Laura Formenti, Massimo Russo, Edoardo Arrigoni, Ferdinando Chiaradonna, Giovanna Chiorino, Giulio Draetta, Joseph R. Marszalek, Christopher P. Vellano, Roberta Pastorelli, MariaRosa Bani, Alessandra Decio, Raffaella Giavazzi, Ghilardi, C, Moreira Barbosa, C, Brunelli, L, Ostano, P, Panini, N, Lupi, M, Anastasia, A, Fiordaliso, F, Salio, M, Formenti, L, Russo, M, Arrigoni, E, Chiaradonna, F, Chiorino, G, Draetta, G, Marszalek, J, Vellano, C, Pastorelli, R, Bani, M, Decio, A, and Giavazzi, R
- Subjects
Ovarian Neoplasms ,Mice ,Cancer Research ,Oncology ,Ovarian cancer, xenograft models, oxphos inhibition, predictive biomarkers, pharmacological response ,Animals ,Humans ,RNA-Binding Proteins ,Female ,Oxidation-Reduction ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Oxidative Phosphorylation ,Mitochondria - Abstract
Ovarian cancer is the deadliest gynecologic cancer, and novel therapeutic options are crucial to improve overall survival. Here we provide evidence that impairment of oxidative phosphorylation (OXPHOS) can help control ovarian cancer progression, and this benefit correlates with expression of the two mitochondrial master regulators PGC1α and PGC1β. In orthotopic patient-derived ovarian cancer xenografts (OC-PDX), concomitant high expression of PGC1α and PGC1β (PGC1α/β) fostered a unique transcriptional signature, leading to increased mitochondrial abundance, enhanced tricarboxylic acid cycling, and elevated cellular respiration that ultimately conferred vulnerability to OXPHOS inhibition. Treatment with the respiratory chain complex I inhibitor IACS-010759 caused mitochondrial swelling and ATP depletion that consequently delayed malignant progression and prolonged the lifespan of high PGC1α/β-expressing OC-PDX-bearing mice. Conversely, low PGC1α/β OC-PDXs were not affected by IACS-010759, thus pinpointing a selective antitumor effect of OXPHOS inhibition. The clinical relevance of these findings was substantiated by analysis of ovarian cancer patient datasets, which showed that 25% of all cases displayed high PGC1α/β expression along with an activated mitochondrial gene program. This study endorses the use of OXPHOS inhibitors to manage ovarian cancer and identifies the high expression of both PGC1α and β as biomarkers to refine the selection of patients likely to benefit most from this therapy. Significance: OXPHOS inhibition in ovarian cancer can exploit the metabolic vulnerabilities conferred by high PGC1α/β expression and offers an effective approach to manage patients on the basis of PGC1α/β expression.
- Published
- 2022
28. A morphological classification of the fat particles found in the urinary sediment of patients with Fabry disease
- Author
-
Dario Consonni, Piergiorgio Messa, Fabio Fiordaliso, Giuseppe Garigali, Alessandro Corbelli, Federico Pieruzzi, Giovanni B. Fogazzi, Fogazzi, G, Garigali, G, Pieruzzi, F, Corbelli, A, Fiordaliso, F, Consonni, D, and Messa, P
- Subjects
Pathology ,medicine.medical_specialty ,Morphology (linguistics) ,Phase contrast microscopy ,Clinical Biochemistry ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,law.invention ,urinary microscopy ,03 medical and health sciences ,0302 clinical medicine ,law ,Urinary sediment ,urinary lipid ,medicine ,Humans ,Microscopy, Phase-Contrast ,Fabry disease ,Polarized light microscopy ,Chemistry ,Biochemistry (medical) ,General Medicine ,medicine.disease ,urinalysi ,Kidney Diseases ,urinary sediment - Abstract
Objectives The search in the urinary sediment (U-sed) of fat particles with peculiar morphology is a simple and inexpensive tool for the diagnosis of Fabry disease (FD) nephropathy. In this study we investigated the morphology of a high number of such fat particles with the aim to obtain a morphological classification to be used for their identification. Methods Study of the morphology of fat particles in the U-sed of a cohort of FD patients using: bright field plus phase contrast microscopy (BF + PC), polarized light microscopy (POL), and transmission electron microscopy (TEM). Comparison of these results with those obtained for the fat particles seen in the U-sed of a control group (CG) of patients with non-FD glomerulopathies. Results FD: 18 U-sed from six patients (three samples/patient) were prospectively investigated and 506 fat particles identified. With BF + PC, these were classified in eight morphological categories (seven of which were confirmed by TEM), and with POL in 10 others. CG: eight U-sed from eight patients were investigated and 281 fat particles identified. These fell into four BF + PC morphological categories and into eight POL categories. While some categories were significantly more frequent in FD others were more frequent in the CG. Conclusions Our study demonstrates that 1. The morphology of fat particles found in the U-sed of FD patients is much wider and complex than that described so far 2. Several significant differences exist in the morphology of such fat particles between FD and CG patients.
- Published
- 2021
29. Mutant Prion Protein Expression Causes Motor and Memory Deficits and Abnormal Sleep Patterns in a Transgenic Mouse Model
- Author
-
Sara Dossena, Michela Mangieri, Claudia Balducci, Assunta Senatore, Loris L. Ferrari, Fabrizio Tagliavini, Mirjana Carli, Luana Fioriti, Susanna Bianchi, Luca Imeri, Fabio Fiordaliso, Gianluigi Forloni, Anna Garofoli, Elena Restelli, Alessandro Pincherle, Michela Morbin, Flavio Villani, Roberto Chiesa, Monica Salio, Gabriella Marcon, Balducci, C, Bianchi, S, Carli, M, Chiesa, R, Dossena, S, Ferrari, L, Fiordaliso, F, Fioriti, L, Forloni, G, Garofoli, A, Imeri, L, Mangeri, M, Marcon, Gabriella, Morbin, M, Pincherle, A, Restelli, E, Salio, M, Senatore, A, Tagliavini, F, and Villani, F.
- Subjects
Sleep Wake Disorders ,Genetically modified mouse ,Prions ,Neuroscience(all) ,animal diseases ,Transgene ,Mutant ,HUMDISEASE ,Mice, Transgenic ,Disease ,Biology ,Endoplasmic Reticulum ,medicine.disease_cause ,Creutzfeldt-Jakob Syndrome ,Mice ,Mutant protein ,mental disorders ,medicine ,Animals ,Evoked Potentials ,Cerebral Cortex ,Memory Disorders ,Mutation ,Movement Disorders ,General Neuroscience ,Endoplasmic reticulum ,Brain ,Electroencephalography ,Virology ,nervous system diseases ,Cell biology ,Mice, Inbred C57BL ,Disease Models, Animal ,Gliosis ,CELLBIO ,medicine.symptom ,SYSNEURO ,Energy Metabolism - Abstract
SummaryA familial form of Creutzfeldt-Jakob disease (CJD) is linked to the D178N/V129 prion protein (PrP) mutation. Tg(CJD) mice expressing the mouse homolog of this mutant PrP synthesize a misfolded form of the mutant protein, which is aggregated and protease resistant. These mice develop clinical and pathological features reminiscent of CJD, including motor dysfunction, memory impairment, cerebral PrP deposition, and gliosis. Tg(CJD) mice also display electroencephalographic abnormalities and severe alterations of sleep-wake patterns strikingly similar to those seen in a human patient carrying the D178N/V129 mutation. Neurons in these mice show swelling of the endoplasmic reticulum (ER) with intracellular retention of mutant PrP, suggesting that ER dysfunction could contribute to the pathology. These results establish a transgenic animal model of a genetic prion disease recapitulating cognitive, motor, and neurophysiological abnormalities of the human disorder. Tg(CJD) mice have the potential for giving greater insight into the spectrum of neuronal dysfunction in prion diseases.
- Published
- 2008
30. Multifunctional liposomes reduce brain β-amyloid burden and ameliorate memory impairment in Alzheimer's disease mouse models
- Author
-
Mario Salmona, Mario Mauri, Fabio Fiordaliso, Emanuele Grigoli, Anniina Snellman, Laura Colombo, Margherita Zotti, Stefania Minniti, Gianluigi Forloni, Giulio Sancini, Simona Mancini, Alfredo Cagnotto, Francesca Re, Pietro La Vitola, Claudia Balducci, Merja Haaparanta-Solin, Massimo Masserini, Balducci, C, Mancini, S, Minniti, S, La Vitola, P, Zotti, M, Sancini, G, Mauri, M, Cagnotto, A, Colombo, L, Fiordaliso, F, Grigoli, E, Salmona, M, Snellman, A, Haaparanta Solin, M, Forloni, G, Masserini, M, and Re, F
- Subjects
Genetically modified mouse ,Male ,Pathology ,medicine.medical_specialty ,Peptide ,Mice, Transgenic ,Plaque, Amyloid ,Pharmacology ,Presenilin ,chemistry.chemical_compound ,Mice ,Random Allocation ,Apolipoproteins E ,Alzheimer Disease ,medicine ,Animals ,chemistry.chemical_classification ,Liposome ,Memory Disorders ,Mice, Inbred BALB C ,Neuroscience (all) ,Amyloid beta-Peptides ,business.industry ,General Neuroscience ,Phosphatidic acid ,Articles ,medicine.disease ,In vitro ,Peptide Fragments ,Mice, Inbred C57BL ,Disease Models, Animal ,Cognitive impairment ,Nanomedicine ,chemistry ,Oligomer ,Liposomes ,Alzheimer ,Abeta ,Alzheimer's disease ,Pittsburgh compound B ,business - Abstract
Alzheimer's disease is characterized by the accumulation and deposition of plaques of β-amyloid (Aβ) peptide in the brain. Given its pivotal role, new therapies targeting Aβ are in demand. We rationally designed liposomes targeting the brain and promoting the disaggregation of Aβ assemblies and evaluated their efficiency in reducing the Aβ burden in Alzheimer's disease mouse models. Liposomes were bifunctionalized with a peptide derived from the apolipoprotein-E receptor-binding domain for blood–brain barrier targeting and with phosphatidic acid for Aβ binding. Bifunctionalized liposomes display the unique ability to hinder the formation of, and disaggregate, Aβ assembliesin vitro(EM experiments). Administration of bifunctionalized liposomes to APP/presenilin 1 transgenic mice (aged 10 months) for 3 weeks (three injections per week) decreased total brain-insoluble Aβ1–42(−33%), assessed by ELISA, and the number and total area of plaques (−34%) detected histologically. Also, brain Aβ oligomers were reduced (−70.5%), as assessed by SDS-PAGE. Plaque reduction was confirmed in APP23 transgenic mice (aged 15 months) either histologically or by PET imaging with [11C]Pittsburgh compound B (PIB). The reduction of brain Aβ was associated with its increase in liver (+18%) and spleen (+20%). Notably, the novel-object recognition test showed that the treatment ameliorated mouse impaired memory. Finally, liposomes reached the brain in an intact form, as determined by confocal microscopy experiments with fluorescently labeled liposomes. These data suggest that bifunctionalized liposomes destabilize brain Aβ aggregates and promote peptide removal across the blood–brain barrier and its peripheral clearance. This all-in-one multitask therapeutic device can be considered as a candidate for the treatment of Alzheimer's disease.
- Published
- 2014
31. Tetracycline and its analogues protect Caenorhabditis elegans from β amyloid-induced toxicity by targeting oligomers
- Author
-
Silvia Maria Doglia, Fabio Fiordaliso, Mario Salmona, Luisa Diomede, Diletta Ami, Giuseppe Cassata, Antonino Natalello, Monica Salio, Ada De Luigi, Diomede, L, Cassata, G, Fiordaliso, F, Salio, M, Ami, D, Natalello, A, Doglia, S, De Luigi, A, and Salmona, M
- Subjects
Amyloid ,Amyloid beta ,Transgene ,FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA) ,Peptide ,Transgenic ,lcsh:RC321-571 ,In vivo ,Alzheimer Disease ,C. elegan ,Animals ,Caenorhabditis elegans ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,chemistry.chemical_classification ,Protein Synthesis Inhibitors ,Amyloid beta-Peptides ,biology ,Dose-Response Relationship, Drug ,P3 peptide ,Brain ,Amyloid beta-peptide ,Alzheimer's disease ,Tetracycline ,biology.organism_classification ,Disease Models, Animal ,Oxidative Stress ,FIS/01 - FISICA SPERIMENTALE ,Neurology ,Proteotoxicity ,Biochemistry ,chemistry ,C. elegans ,biology.protein - Abstract
The accumulation and deposition of amyloid beta (Aβ) peptide in extracellular dense plaques in the brain is a key phase in Alzheimer's disease (AD). Small oligomeric forms of Aβ are responsible for the toxicity and the early cognitive impairment observed in patients before the amyloid plaque deposits appear. It is essential for the development of an efficient cure for AD to identify compounds that interfere with Aβ aggregation, counteracting the molecular mechanisms involved in conversion of the monomeric amyloid protein into oligomeric and fibrillar forms. Tetracyclines have been proposed for AD therapy, although their effects on the aggregation of Aβ protein, particularly their ability to interact in vivo with the Aβ oligomers and/or aggregates, remain to be understood. Using transgenic Caenorhabditis elegans as a simplified invertebrate model of AD, we evaluated the ability of tetracyclines to interfere with the sequence of events leading to Aβ proteotoxicity. The drugs directly interact with the Aβ assemblies in vivo and reduce Aβ oligomer deposition, protecting C. elegans from oxidative stress and the onset of the paralysis phenotype. These effects were specific, dose-related and not linked to any antibiotic activity, suggesting that the drugs might offer an effective therapeutic strategy to target soluble Aβ aggregates.
- Published
- 2010
32. Regression of diabetic complications by islet transplantation in the rat
- Author
-
Marina Figliuzzi, Andrea Remuzzi, F Avezza, Valentina Alda Carozzi, Norberto Oggioni, Roberta Cornolti, Carla Porretta-Serapiglia, Raffaella Lombardi, Roberto Bianchi, Guido Cavaletti, L Crippa, Fabio Fiordaliso, Giuseppe Lauria, M. Salio, Remuzzi, A, Cornolti, R, Bianchi, R, Figliuzzi, M, Porretta Serapiglia, C, Oggioni, N, Carozzi, V, Crippa, L, Avezza, F, Fiordaliso, F, Salio, M, Lauria, G, Lombardi, R, and Cavaletti, G
- Subjects
Blood Glucose ,Male ,Tail ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Islets of Langerhans Transplantation ,Neural Conduction ,Pain ,Gastroenterology ,Thiobarbituric Acid Reactive Substances ,Nephropathy ,Diabetes Complications ,Nerve Fibers ,Diabetic Neuropathies ,Diabetes Complication ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Animals ,Humans ,geography ,Type 1 diabetes ,geography.geographical_feature_category ,Animal ,business.industry ,Nociceptor ,Nociceptors ,Islet ,medicine.disease ,Sciatic Nerve ,Rats ,Transplantation ,Transplantation, Isogeneic ,Endocrinology ,Rats, Inbred Lew ,Thiobarbituric Acid Reactive Substance ,Quality of Life ,Rat ,Diabetic Neuropathie ,Pancreatic islet transplantation ,Sodium-Potassium-Exchanging ATPase ,Complication ,business ,Human ,Kidney disease - Abstract
Type 1 diabetes is a chronic disease leading to complications such as peripheral neuropathies, nephropathy and cardiovascular disease. Pancreatic islet transplantation is being extensively investigated for blood glucose control in animals and in human type 1 diabetic patients, but the question of whether it can reverse long-term diabetic complications has not been fully explored. We investigated the effects of islet transplantation on diabetic complications in a rat model of streptozotocin-induced diabetes.Three groups of rats were used: healthy controls, diabetic and diabetic rats transplanted with microencapsulated islets at 2 months after diabetes induction, when neuropathy was detectable by a decrease in tail nerve conduction velocity (NCV) and impaired nociceptive thresholds. Blood glucose levels and body weight were measured weekly. The variables considered were: thermal (hot plate test) and mechanical sensitivity (Randal-Selitto paw withdrawal test), NCV and Na+, K+-ATPase activity in the sciatic nerve. At the end of the experiments hearts were removed for morphometric determination and myocyte number, and kidneys removed for histological examination.Islet transplantation in diabetic rats induced normoglycaemia in a few days, accompanied by a rapid rise in body weight and amelioration of impaired nociceptive thresholds, as well as normalisation of NCV and Na(+), K(+)-ATPase, which were both about 25% below normal in diabetic rats. Myocyte loss was reduced (-34%) by islet transplantation and the observed mild kidney damage of diabetic rats was prevented.Besides controlling glycaemia, transplantation of microencapsulated pancreatic islets induced almost complete regression of neuropathy and prevented cardiovascular alterations.
- Published
- 2009
33. Eplerenone, a selective Aldosterone Blocker, improves diastolic Function in aged Rats with small-to-moderate myocardial Infarction
- Author
-
Lidia Staszewsky, Beatrice Arosio, Fabio Fiordaliso, Eleonora Carlo, Serge Masson, Eugenio Scanziani, Amy E. Rudolph, Antonio Bai, Giorgio Annoni, Elena Martinoli, Roberto Latini, Monica Salio, Carmen Calabresi, Masson, S, Staszewsky, L, Annoni, G, Carlo, E, Arosio, B, Bai, A, Calabresi, C, Martinoli, E, Salio, M, Fiordaliso, F, Scanziani, E, Rudolph, A, and Latini, R
- Subjects
Male ,medicine.medical_specialty ,Diastole ,Hemodynamics ,Spironolactone ,Kidney ,Ventricular Function, Left ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,echocardiography ,Myocardial infarction ,Rats, Wistar ,Mineralocorticoid Receptor Antagonists ,Analysis of Variance ,Aldosterone ,aldosterone ,business.industry ,Myocardium ,aging ,diastolic function ,medicine.disease ,Eplerenone ,Rats ,aorta ,Treatment Outcome ,myocardial infarction ,chemistry ,Heart failure ,Cardiology ,MED/09 - MEDICINA INTERNA ,Cardiology and Cardiovascular Medicine ,Isovolumic relaxation time ,business ,medicine.drug - Abstract
Background: The incidence of cardiovascular diseases increases rapidly with age, and the elderly suffer higher morbidity and mortality. Aldosterone blockers have shown. benefits in patients with left ventricular (LV) dysfunction and heart failure after myocardial infarction (MI). However, aldosterone blockade efficacy has not been explored in aged animals with MI. Methods and Results: Small-to-moderate MI was induced by coronary artery ligation in 16-month old rats, divided into 3 groups: sham-operated (control, n = 9), MI (n. = 9), and MI fed a diet containing eplerenone (120 mg/kg/day, MI+Eplerenone, n = 9). given 18 days postsurgery and up to sacrifice 3 months later. At. sacrifice, untreated MI rats did not show overt systolic dysfunctiom but they had (1) echocardiographic evidences of impaired relaxation (increase of E wave deceleration time and of isovolumic relaxation time, decrease of peak E wave velocity), (2) hemodynamically impaired LV relaxation (LV -dP/dt from 7413 +/- 720 to 4956 +/- 475 mm Hg/s, P < .05), and (3) significant increase of collagen content in LV interstitium (from 4.27 +/- 0.23 to 5.34 +/- 0.24%, P < .01), and in aorta. (from 19 +/- 1 to 24 +/- 2%, P < .05). Eplerenone normalized echocardiographic and hemodynamic evidences of diastolic dysfunction, as well as myocardial. interstitial collagen and aortic fibrosis. (all parameters statistically different from untreated MI). Conclusion: In aged rats with small to moderate MI, eplerenone normalized diastolic relaxation, possibly through a reduction of interstitial fibrosis.
- Published
- 2004
34. Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor
- Author
-
Anthony Cerami, Thomas Coleman, Fabio Fiordaliso, Pietro Ghezzi, Daniel Gomez, Eileen Pobre, Roberto Latini, Maddalena Fratelli, Michael Brines, Qiao wen Xie, Deborah Diaz, Giovanni Grasso, Alessandra Sfacteria, Carla Hand, Chiao Ju Su-Rick, John Smart, BRINES M, GRASSO G, FIORDALISO F, SFACTERIA A, GHEZZI P, FRATELLI M, LATINI R, XIE QW, SMART J, SU-RICK CJ, POBRE E, DIAZ D, GOMEZ D, HAND C, COLEMAN T, and CERAMI A
- Subjects
Time Factors ,Biology ,Motor Activity ,Heteroreceptor ,Neuroprotection ,Cell Line ,Mice ,medicine ,Receptors, Erythropoietin ,Animals ,Ventricular Function ,erythropoietin receptor ,common beta receptor ,tissue injury ,Cytokines ,Receptor ,Erythropoietin ,Aorta ,Cells, Cultured ,Spinal Cord Injuries ,Mice, Knockout ,Multidisciplinary ,Cell Membrane ,Biological Sciences ,Erythropoietin, Erythropoietin receptor, neuroprotection ,Erythropoietin receptor ,Cell biology ,Mice, Inbred C57BL ,Protein Subunits ,Erythrocyte maturation ,Knockout mouse ,Immunology ,Erythropoiesis ,medicine.drug - Abstract
The cytokine erythropoietin (Epo) is tissue-protective in preclinical models of ischemic, traumatic, toxic, and inflammatory injuries. We have recently characterized Epo derivatives that do not bind to the Epo receptor (EpoR) yet are tissue-protective. For example, carbamylated Epo (CEpo) does not stimulate erythropoiesis, yet it prevents tissue injury in a wide variety ofin vivoandin vitromodels. These observations suggest that another receptor is responsible for the tissue-protective actions of Epo. Notably, prior investigation suggests that EpoR physically interacts with the common β receptor (βcR), the signal-transducing subunit shared by the granulocyte-macrophage colony stimulating factor, and the IL-3 and IL-5 receptors. However, because βcR knockout mice exhibit normal erythrocyte maturation, βcR is not required for erythropoiesis. We hypothesized that βcR in combination with the EpoR expressed by nonhematopoietic cells constitutes a tissue-protective receptor. In support of this hypothesis, membrane proteins prepared from rat brain, heart, liver, or kidney were greatly enriched in EpoR after passage over either Epo or CEpo columns but covalently bound in a complex with βcR. Further, antibodies against EpoR coimmunoprecipitated βcR from membranes prepared from neuronal-like P-19 cells that respond to Epo-induced tissue protection. Immunocytochemical studies of spinal cord neurons and cardiomyocytes protected by Epo demonstrated cellular colocalization of Epo βcR and EpoR. Finally, as predicted by the hypothesis, neither Epo nor CEpo was active in cardiomyocyte or spinal cord injury models performed in the βcR knockout mouse. These data support the concept that EpoR and βcR comprise a tissue-protective heteroreceptor.
- Published
- 2004
35. Left ventricular Response to beta-adrenergic Stimulation in aging Rats
- Author
-
Carlo Vergani, Laura Calvillo, Serge Masson, Fabio Fiordaliso, Beatrice Arosio, Silvia D'Aquila, D. Santambrogio, Nicoletta Gagliano, Giorgio Annoni, Roberto Latini, Masson, S, Arosio, B, Fiordaliso, F, Gagliano, N, Calvillo, L, Santambrogio, D, D'Aquila, S, Vergani, C, Latini, R, and Annoni, G
- Subjects
Male ,Aging ,medicine.medical_specialty ,Sympathetic nervous system ,ISOPRENALINE ,Population ,Cardiomegaly ,Stimulation ,UP-REGULATION ,Ventricular Function, Left ,AGE ,Atrial natriuretic peptide ,Heart Rate ,Transforming Growth Factor beta ,Fibrosis ,Internal medicine ,medicine ,EXTRACELLULAR-MATRIX ,Animals ,Myocyte ,Rats, Wistar ,education ,GENE-EXPRESSION ,Analysis of Variance ,education.field_of_study ,INDUCED CARDIAC-HYPERTROPHY ,business.industry ,Isoproterenol ,CELL-MATRIX INTERACTIONS ,Adrenergic beta-Agonists ,Blotting, Northern ,medicine.disease ,Adaptation, Physiological ,COLLAGEN ,Rats ,Procollagen peptidase ,Endocrinology ,medicine.anatomical_structure ,Gene Expression Regulation ,Heart failure ,HEART-FAILURE ,Geriatrics and Gerontology ,MED/09 - MEDICINA INTERNA ,business ,MYOCARDIUM ,Atrial Natriuretic Factor - Abstract
The incidence of heart failure in the population increases steeply among older people. Overactivation of the sympathetic nervous system is associated to and responsible for worsening of heart failure. This study describes the influence of aging on short-term left ventricular (LV) adaptation to b-adrenergic stimulation in Wistar rats. In controls at 18 mo, interstitial fibrosis was increased with respect to 3-mo-old rats, whereas myocytes dimension and the messenger RNA (mRNA) abundance of atrial natriuretic peptide (ANP), a2 (I) procollagen, transforming growth factor (TGF-b,, TGFb3), and secreted protein, acidic and rich in cysteine (SPARC) were not different. To determine how aging affects LV adaptation to adrenergic stimulation, two groups of animals received isoproterenol (ISO, 1 mg/kg/d) for 3 days. There was no significant difference between young and older rats with respect to increase in LV weight, myocytes dimension, and mRNA abundance of all the genes considered, except a,(111) procollagen. These findings indicate that despite limited compensatory hypertrophy and higher fibrosis, LV from aged nonsenescent rats preserves the capacity to adapt to b-adrenergic stimulation through the upregulation of several genes encoding extracellular matrix-related proteins. 'T'HE incidence of cardiovascular diseases, and ultimately J_ heart failure, increases steeply with age (1), with greater detrimental impact on the elderly population that suffers higher morbidity and mortality (2,3). Overactivation of the sympathetic nervous system is associated with and responsible for worsening of heart failure, a setting where (3-blockers have been proved beneficial (4). The aging heart is characterized, in both humans and rats, by a progressive loss of myocytes partially compensated by cellular enlargement, collagen accumulation in the interstitium, and arterial stiffening (5-8). The aging heart has also a diminished capacity to respond to stressful situations. In particular, the sympathetic modulation of cardiovascular function declines with age in humans and in experimental models (9). At the molecular level, for instance, the expression of several protooncogenes upregulated very early during the cardiac hypertrophic response to |3-adrenergic stimulation is blunted in aged animals (10). Information is scant, however, about how the aged heart adapts to (3-adrenergic stimulation through remodeling of the extracellular matrix (ECM). This structure is important not only because it maintains ventricular
- Published
- 2000
36. Evolution of Nanoparticle Protein Corona across the Blood–Brain Barrier
- Author
-
Francesca Re, Fabio Fiordaliso, Francesca Raimondo, Clizia Chinello, Alysia Cox, Laura Talamini, Francesco Stellacci, Patrizia Andreozzi, Massimo Masserini, Fulvio Magni, Roberta Dal Magro, Alessandro Corbelli, Paulo Jacob Silva, Silke Krol, Maria Tringali, Cox, A, Andreozzi, P, Dal Magro, R, Fiordaliso, F, Corbelli, A, Talamini, L, Chinello, C, Raimondo, F, Magni, F, Tringali, M, Krol, S, Jacob Silva, P, Stellacci, F, Masserini, M, and Re, F
- Subjects
0301 basic medicine ,endocrine system ,brain ,General Physics and Astronomy ,Nanoparticle ,Protein Corona ,02 engineering and technology ,Blood–brain barrier ,Physics and Astronomy (all) ,03 medical and health sciences ,protein corona ,Engineering (all) ,medicine ,Biological fluids ,Humans ,General Materials Science ,biological barrier ,Drug transport ,Chemistry ,nanoparticle ,General Engineering ,Endothelial Cells ,blood-brain barrier ,021001 nanoscience & nanotechnology ,BIO/10 - BIOCHIMICA ,Engineered nanoparticles ,030104 developmental biology ,medicine.anatomical_structure ,Colloidal gold ,Blood circulation ,Biophysics ,Nanoparticles ,Materials Science (all) ,0210 nano-technology - Abstract
Engineered nanoparticles offer the chance to improve drug transport and delivery through biological barriers, exploiting the possibility to leave the blood circulation and traverse the endothelial vascular bed, blood-brain barrier (BBB) included, to reach their target. It is known that nanoparticles gather molecules on their surface upon contact with biological fluids, forming the "protein corona", which can affect their fate and therapeutic/diagnostic performance, yet no information on the corona's evolution across the barrier has been gathered so far. Using a cellular model of the BBB and gold nanoparticles, we show that the composition of the corona undergoes dramatic quantitative and qualitative molecular modifications during passage from the "blood" to the "brain" side, while it is stable once beyond the BBB. Thus, we demonstrate that the nanoparticle corona dynamically and drastically evolves upon crossing the BBB and that its initial composition is not predictive of nanoparticle fate and performance once beyond the barrier at the target organ.
- Full Text
- View/download PDF
37. Ageing and the molecular and structural remodelling of cardiac extracellular matrix during β-adrenergic stimulation
- Author
-
Giorgio Annoni, Nicoletta Gagliano, L. Calvillo, F. Flordaliso, D. Santambrogio, B. Aroalo, S. Maason, Roberto Latini, Maason, S, Arosio, B, Fiordaliso, F, Gagliano, N, Santambrogio, D, Calvillo, L, Latini, R, and Annoni, G
- Subjects
Extracellular matrix ,Ageing ,business.industry ,Medicine ,β adrenergic stimulation ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business ,Cell biology - Full Text
- View/download PDF
38. Thermal effects and biological response of breast and pancreatic cancer cells undergoing gold nanorod-assisted photothermal therapy.
- Author
-
Bianchi L, Baroni S, Paroni G, Violatto MB, Moscatiello GY, Panini N, Russo L, Fiordaliso F, Colombo L, Diomede L, Saccomandi P, and Bigini P
- Subjects
- Humans, Cell Line, Tumor, Female, Animals, Mice, Breast Neoplasms therapy, Breast Neoplasms pathology, Temperature, Phototherapy, Gold chemistry, Nanotubes chemistry, Pancreatic Neoplasms therapy, Pancreatic Neoplasms pathology, Photothermal Therapy, Cell Survival drug effects, Cell Survival radiation effects, Infrared Rays
- Abstract
To increase the therapeutic efficacy of nanoparticle (NP)-assisted photothermal therapy (PTT) and allow for a transition toward the clinical setting, it is pivotal to characterize the thermal effect induced in cancer cells and correlate it with the cell biological response, namely cell viability and cell death pathways. This study quantitatively evaluated the effects of gold nanorod (GNR)-assisted near-infrared (NIR) PTT on two different cancer cell lines, the 4T1 triple-negative breast cancer cells and the Pan02 pancreatic cancer cells. The interaction between nanomaterials and biological matrices was investigated in terms of GNR internalization and effect on cell viability at different GNR concentrations. GNR-mediated PTT was executed on both cell lines, at the same treatment settings to allow a straightforward comparison, and real-time monitored through thermographic imaging. A thermal analysis based on various parameters (i.e., maximum absolute temperature, maximum temperature change, temperature variation profile, area under the time-temperature change curve, effective thermal enhancement (ETE), and time constants) was performed to evaluate the treatment thermal outcome. While GNR treatment and NIR laser irradiation alone did not cause cell toxicity in the selected settings, their combination induced a significant reduction of cell viability in both cell lines. At the optimal experimental condition (i.e., 6 μg/mL of GNRs and 4.5 W/cm
2 laser power density), GNR-assisted PTT reduced the cell viability of 4T1 and Pan02 cells by 94% and 87% and it was associated with maximum temperature changes of 25 °C and 29 °C (i.e., ∼1.8-fold increase compared to the laser-only condition), maximum absolute temperatures of 55 °C and 54 °C, and ETE values of 78% and 81%, for 4T1 and Pan02 cells, correspondingly. Also, the increase in the GNR concentration led to a decrease in the time constants, denoting faster heating kinetics upon irradiation. Furthermore, the thermal analysis parameters were correlated with the extent of cell death. Twelve hours after NIR exposure, GNR-assisted PTT was found to mainly trigger secondary apoptosis in both cell lines. The proposed study provides relevant insights into the relationship between temperature history and biological responses in the context of PTT. The findings contribute to the development of a universal methodology for evaluating thermal sensitivity upon NP-assisted PTT on different cell types and lay the groundwork for future translational studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
39. Fenofibrate reduces cardiac remodeling by mitochondrial dynamics preservation in a renovascular model of cardiac hypertrophy.
- Author
-
Castiglioni L, Gelosa P, Muluhie M, Mercuriali B, Rzemieniec J, Gotti M, Fiordaliso F, Busca G, and Sironi L
- Subjects
- Animals, Male, Rats, Autophagy drug effects, Hypertension, Renovascular drug therapy, Hypertension, Renovascular metabolism, Hypertension, Renovascular pathology, Hypertension, Renovascular physiopathology, Rats, Wistar, Blood Pressure drug effects, Fenofibrate pharmacology, Fenofibrate therapeutic use, Mitochondrial Dynamics drug effects, Cardiomegaly drug therapy, Cardiomegaly metabolism, Cardiomegaly pathology, Myocytes, Cardiac drug effects, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, Disease Models, Animal, Ventricular Remodeling drug effects
- Abstract
Fenofibrate, a PPAR-α agonist clinically used to lower serum lipid levels, reduces cardiac remodeling and improves cardiac function. However, its mechanism of action is not completely elucidated. In this study we examined the effect of fenofibrate on mitochondria in a rat model of renovascular hypertension, focusing on mediators controlling mitochondrial dynamics and autophagy. Rats with two-kidney one-clip (2K1C) hypertension were treated with fenofibrate 150 mg/kg/day (2K1C-FFB) or vehicle (2K1C-VEH) for 8 weeks. Systolic blood pressure and cardiac functional were in-vivo assessed, while cardiomyocyte size and protein expression of mediators of cardiac hypertrophy and mitochondrial dynamics were ex-vivo examined by histological and Western blot analyses. Fenofibrate treatment counteracted the development of hypertension and the increase of left ventricular mass, relative wall thickness and cross-sectional area of cardiomyocytes. Furthermore, fenofibrate re-balanced the expression Mfn2, Drp1 and Parkin, regulators of fusion, fission, mitophagy respectively. Regarding autophagy, the LC3-II/LC3-I ratio was increased in 2K1C-VEH and 2K1C-FFB, whereas the autophagy was increased only in 2K1C-FFB. In cultured H9C2 cardiomyoblasts, fenofibrate reversed the Ang II-induced mRNA up-regulation of hypertrophy markers Nppa and Myh7, accumulation of reactive oxygen species and depolarization of the mitochondrial membrane exerting protection mediated by up-regulation of the Uncoupling protein 2. Our results indicate that fenofibrate acts directly on cardiomyocytes and counteracts the pressure overload-induced cardiac maladaptive remodeling. This study reveals a so far hidden mechanism involving mitochondrial dynamics in the beneficial effects of fenofibrate, support its repurposing for the treatment of cardiac hypertrophy and provide new potential targets for its pharmacological function., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luigi Sironi reports financial support was provided by University of Milan. Luigi Sironi reports a relationship with University of Milan that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
40. Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis.
- Author
-
Schulte T, Chaves-Sanjuan A, Speranzini V, Sicking K, Milazzo M, Mazzini G, Rognoni P, Caminito S, Milani P, Marabelli C, Corbelli A, Diomede L, Fiordaliso F, Anastasia L, Pappone C, Merlini G, Bolognesi M, Nuvolone M, Fernández-Busnadiego R, Palladini G, and Ricagno S
- Subjects
- Humans, Collagen metabolism, Collagen ultrastructure, Collagen chemistry, Middle Aged, Amyloidosis metabolism, Amyloidosis pathology, Male, Cryoelectron Microscopy, Amyloid metabolism, Amyloid chemistry, Amyloid ultrastructure, Immunoglobulin Light-chain Amyloidosis metabolism, Immunoglobulin Light-chain Amyloidosis pathology, Myocardium metabolism, Myocardium pathology, Myocardium ultrastructure
- Abstract
Systemic light chain (LC) amyloidosis (AL) is a disease where organs are damaged by an overload of a misfolded patient-specific antibody-derived LC, secreted by an abnormal B cell clone. The high LC concentration in the blood leads to amyloid deposition at organ sites. Indeed, cryogenic electron microscopy (cryo-EM) has revealed unique amyloid folds for heart-derived fibrils taken from different patients. Here, we present the cryo-EM structure of heart-derived AL amyloid (AL59) from another patient with severe cardiac involvement. The double-layered structure displays a u-shaped core that is closed by a β-arc lid and extended by a straight tail. Noteworthy, the fibril harbours an extended constant domain fragment, thus ruling out the variable domain as sole amyloid building block. Surprisingly, the fibrils were abundantly concatenated with a proteinaceous polymer, here identified as collagen VI (COLVI) by immuno-electron microscopy (IEM) and mass-spectrometry. Cryogenic electron tomography (cryo-ET) showed how COLVI wraps around the amyloid forming a helical superstructure, likely stabilizing and protecting the fibrils from clearance. Thus, here we report structural evidence of interactions between amyloid and collagen, potentially signifying a distinct pathophysiological mechanism of amyloid deposits., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
41. Different Patterns of Platinum Resistance in Ovarian Cancer Cells with Homologous Recombination Proficient and Deficient Background.
- Author
-
Chiappa M, Guffanti F, Grasselli C, Panini N, Corbelli A, Fiordaliso F, and Damia G
- Subjects
- Humans, Female, Animals, Mice, Platinum, Neoplasm Recurrence, Local, Homologous Recombination, Drug Resistance, Neoplasm, Cell Line, Tumor, Cisplatin pharmacology, Ovarian Neoplasms metabolism
- Abstract
Platinum compounds are very active in first-line treatments of ovarian carcinoma. In fact, high rates of complete remission are achieved, but most patients eventually relapse with resistant disease. Many mechanisms underlying the platinum-resistant phenotype have been reported. However, there are no data in the same isogenic cell system proficient and deficient in homologous recombination (HR) on platinum-acquired resistance that might unequivocally clarify the most important mechanism associated with resistance. We generated and characterized cisplatin (DDP)-resistant murine ovarian ID8 cell lines in a HR-deficient and -proficient background. Specific upregulation of the NER pathway in the HR-proficient and -resistant cells and partial restoration of HR in Brca1-/--resistant cells were found. Combinations of different inhibitors of the DNA damage response pathways with cisplatin were strongly active in both resistant and parental cells. The data from the ID8 isogenic system are in line with current experimental and clinical evidence and strongly suggest that platinum resistance develops in different ways depending on the cell DNA repair status (i.e., HR-proficient or HR-deficient), and the upregulation and/or restoration of repair pathways are major determinants of DDP resistance.
- Published
- 2024
- Full Text
- View/download PDF
42. Long-term retention of gold nanoparticles in the liver is not affected by their physicochemical characteristics.
- Author
-
Fernandez Alarcon J, Soliman M, Lüdtke TU, Clemente E, Dobricic M, Violatto MB, Corbelli A, Fiordaliso F, Cordiglieri C, Talamini L, Sitia G, Moya S, Bigini P, and Monopoli MP
- Subjects
- Mice, Animals, Endothelial Cells, Liver, Kupffer Cells, Gold toxicity, Metal Nanoparticles toxicity
- Abstract
Gold nanoparticles (GNPs) are considered promising candidates for healthcare applications, however, their toxicity after long-term exposure to the material remains uncertain. Since the liver is the main filter organ for nanomaterials, this work was aimed at evaluating hepatic accumulation, internalisation and overall safety of well-characterised and endotoxin-free GNPs in healthy mice from 15 minutes to 7 weeks after a single administration. Our data demonstrate that GNPs were rapidly segregated into lysosomes of endothelial cells (LSEC) or Kupffer cells regardless of coating or shape but with different kinetics. Despite the long-lasting accumulation in tissues, the safety of GNPs was confirmed by liver enzymatic levels, as they were rapidly eliminated from the blood circulation and accumulated in the liver without inducing hepatic toxicity. Our results demonstrate that GNPs have a safe and biocompatibile profile despite their long-term accumulation.
- Published
- 2023
- Full Text
- View/download PDF
43. Exploiting endocytosis for transfection of mRNA for cytoplasmatic delivery using cationic gold nanoparticles.
- Author
-
Gustà MF, Edel MJ, Salazar VA, Alvarez-Palomo B, Juan M, Broggini M, Damia G, Bigini P, Corbelli A, Fiordaliso F, Barbul A, Korenstein R, Bastús NG, and Puntes V
- Subjects
- RNA, Messenger, Transfection, Endocytosis, Gold, Metal Nanoparticles
- Abstract
Introduction: Gene therapy holds promise to cure various diseases at the fundamental level. For that, efficient carriers are needed for successful gene delivery. Synthetic 'non-viral' vectors, as cationic polymers, are quickly gaining popularity as efficient vectors for transmitting genes. However, they suffer from high toxicity associated with the permeation and poration of the cell membrane. This toxic aspect can be eliminated by nanoconjugation. Still, results suggest that optimising the oligonucleotide complexation, ultimately determined by the size and charge of the nanovector, is not the only barrier to efficient gene delivery., Methods: We herein develop a comprehensive nanovector catalogue comprising different sizes of Au NPs functionalized with two different cationic molecules and further loaded with mRNA for its delivery inside the cell., Results and Discussion: Tested nanovectors showed safe and sustained transfection efficiencies over 7 days, where 50 nm Au NPs displayed the highest transfection rates. Remarkably, protein expression was increased when nanovector transfection was performed combined with chloroquine. Cytotoxicity and risk assessment demonstrated that nanovectors are safe, ascribed to lesser cellular damage due to their internalization and delivery via endocytosis. Obtained results may pave the way to design advanced and efficient gene therapies for safely transferring oligonucleotides., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gustà, Edel, Salazar, Alvarez-Palomo, Juan, Broggini, Damia, Bigini, Corbelli, Fiordaliso, Barbul, Korenstein, Bastús and Puntes.)
- Published
- 2023
- Full Text
- View/download PDF
44. Food-Grade Titanium Dioxide Induces Toxicity in the Nematode Caenorhabditis elegans and Acute Hepatic and Pulmonary Responses in Mice.
- Author
-
Sitia G, Fiordaliso F, Violatto MB, Alarcon JF, Talamini L, Corbelli A, Ferreira LM, Tran NL, Chakraborty I, Salmona M, Parak WJ, Diomede L, and Bigini P
- Abstract
Food-grade titanium dioxide (E171) contains variable percentages of titanium dioxide (TiO
2 ) nanoparticles (NPs), posing concerns for its potential effects on human and animal health. Despite many studies, the actual relationship between the physicochemical properties of E171 NPs and their interaction with biological targets is still far from clear. We evaluated the impact of acute E171 administration on invertebrate and vertebrate animals. In the nematode, Caenorhabditis elegans , the administration of up to 1.0 mg/mL of E171 did not affect the worm's viability and lifespan, but significantly impaired its pharyngeal function, reproduction, and development. We also investigated whether the intravenous administration of E171 in mice (at the dose of 6 mg/kg/body weight) could result in an acute over-absorption of filter organs. A significant increase of hepatic titanium concentration and the formation of microgranulomas were observed. Interstitial inflammation and parenchymal modification were found in the lungs, coupled with titanium accumulation. This was probably due to the propensity of TiO2 NPs to agglomerate, as demonstrated by transmission electron microscopy experiments showing that the incubation of E171 with serum promoted the formation of compact clusters. Overall, these data emphasize the actual risk for human and animal exposure to E171.- Published
- 2022
- Full Text
- View/download PDF
45. PGC1α/β Expression Predicts Therapeutic Response to Oxidative Phosphorylation Inhibition in Ovarian Cancer.
- Author
-
Ghilardi C, Moreira-Barbosa C, Brunelli L, Ostano P, Panini N, Lupi M, Anastasia A, Fiordaliso F, Salio M, Formenti L, Russo M, Arrigoni E, Chiaradonna F, Chiorino G, Draetta G, Marszalek JR, Vellano CP, Pastorelli R, Bani M, Decio A, and Giavazzi R
- Subjects
- Animals, Female, Humans, Mice, Mitochondria metabolism, Oxidation-Reduction, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics, Ovarian Neoplasms metabolism, Oxidative Phosphorylation, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism, RNA-Binding Proteins metabolism
- Abstract
Ovarian cancer is the deadliest gynecologic cancer, and novel therapeutic options are crucial to improve overall survival. Here we provide evidence that impairment of oxidative phosphorylation (OXPHOS) can help control ovarian cancer progression, and this benefit correlates with expression of the two mitochondrial master regulators PGC1α and PGC1β. In orthotopic patient-derived ovarian cancer xenografts (OC-PDX), concomitant high expression of PGC1α and PGC1β (PGC1α/β) fostered a unique transcriptional signature, leading to increased mitochondrial abundance, enhanced tricarboxylic acid cycling, and elevated cellular respiration that ultimately conferred vulnerability to OXPHOS inhibition. Treatment with the respiratory chain complex I inhibitor IACS-010759 caused mitochondrial swelling and ATP depletion that consequently delayed malignant progression and prolonged the lifespan of high PGC1α/β-expressing OC-PDX-bearing mice. Conversely, low PGC1α/β OC-PDXs were not affected by IACS-010759, thus pinpointing a selective antitumor effect of OXPHOS inhibition. The clinical relevance of these findings was substantiated by analysis of ovarian cancer patient datasets, which showed that 25% of all cases displayed high PGC1α/β expression along with an activated mitochondrial gene program. This study endorses the use of OXPHOS inhibitors to manage ovarian cancer and identifies the high expression of both PGC1α and β as biomarkers to refine the selection of patients likely to benefit most from this therapy., Significance: OXPHOS inhibition in ovarian cancer can exploit the metabolic vulnerabilities conferred by high PGC1α/β expression and offers an effective approach to manage patients on the basis of PGC1α/β expression., (©2022 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2022
- Full Text
- View/download PDF
46. Self-reported smell and taste recovery in coronavirus disease 2019 patients: a one-year prospective study.
- Author
-
Boscolo-Rizzo P, Guida F, Polesel J, Marcuzzo AV, Antonucci P, Capriotti V, Sacchet E, Cragnolini F, D'Alessandro A, Zanelli E, Marzolino R, Lazzarin C, Tofanelli M, Gardenal N, Borsetto D, Hopkins C, Vaira LA, and Tirelli G
- Subjects
- Humans, Prospective Studies, SARS-CoV-2, Self Report, Smell, Taste, Taste Disorders diagnosis, Taste Disorders epidemiology, Taste Disorders etiology, COVID-19, Olfaction Disorders epidemiology, Olfaction Disorders etiology
- Abstract
Purpose: The aim of the present study was to estimate the 1 year prevalence and recovery rate of self-reported chemosensory dysfunction in a series of subjects with previous mild-to-moderate symptomatic COVID-19., Methods: Prospective study based on the SNOT-22, item "sense of smell or taste" and additional outcomes., Results: 268/315 patients (85.1%) completing the survey at baseline also completed the follow-up interview. The 12 months prevalence of self-reported COVID-19 associated chemosensory dysfunction was 21.3% (95% CI 16.5-26.7%). Of the 187 patients who complained of COVID-19 associated chemosensory dysfunction at baseline, 130 (69.5%; 95% CI 62.4-76.0%) reported complete resolution of smell or taste impairment, 41 (21.9%) reported a decrease in the severity, and 16 (8.6%) reported the symptom was unchanged or worse 1 year after onset. The risk of persistence was higher for patients reporting a baseline SNOT-22 score ≥ 4 (OR = 3.32; 95% CI 1.32-8.36) as well as for those requiring ≥ 22 days for a negative swab (OR = 2.18; 95% CI 1.12-4.27)., Conclusion: A substantial proportion of patients with previous mild-to-moderate symptomatic COVID-19 characterized by new onset of chemosensory dysfunction still complained on altered sense of smell or taste 1 year after the onset., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
47. Deletion of calcineurin from astrocytes reproduces proteome signature of Alzheimer's disease and epilepsy and predisposes to seizures.
- Author
-
Tapella L, Dematteis G, Ruffinatti FA, Ponzoni L, Fiordaliso F, Corbelli A, Albanese E, Pistolato B, Pagano J, Barberis E, Marengo E, Balducci C, Forloni G, Verpelli C, Sala C, Distasi C, Sala M, Manfredi M, Genazzani AA, and Lim D
- Subjects
- Animals, Astrocytes, Calcineurin, Mice, Neuroinflammatory Diseases, Proteome, Proteomics, Seizures genetics, Alzheimer Disease genetics, Epilepsy genetics
- Abstract
Calcineurin (CaN), acting downstream of intracellular calcium signals, orchestrates cellular remodeling in many cellular types. In astrocytes, major homeostatic players in the central nervous system (CNS), CaN is involved in neuroinflammation and gliosis, while its role in healthy CNS or in early neuro-pathogenesis is poorly understood. Here we report that in mice with conditional deletion of CaN in GFAP-expressing astrocytes (astroglial calcineurin KO, ACN-KO), at 1 month of age, transcription was largely unchanged, while the proteome was deranged in the hippocampus and cerebellum. Gene ontology analysis revealed overrepresentation of annotations related to myelin sheath, mitochondria, ribosome and cytoskeleton. Over-represented pathways were related to protein synthesis, oxidative phosphorylation, mTOR and neurological disorders, including Alzheimer's disease (AD) and seizure disorder. Comparison with published proteomic datasets showed significant overlap with the proteome of a familial AD mouse model and of human subjects with drug-resistant seizures. ACN-KO mice showed no alterations of motor activity, equilibrium, anxiety or depressive state. However, in Barnes maze ACN-KO mice learned the task but adopted serial search strategy. Strikingly, beginning from about 5 months of age ACN-KO mice developed spontaneous tonic-clonic seizures with an inflammatory signature of epileptic brains. Altogether, our data suggest that the deletion of astroglial CaN produces features of neurological disorders and predisposes mice to seizures. We suggest that calcineurin in astrocytes may serve as a novel Ca
2+ -sensitive switch which regulates protein expression and homeostasis in the central nervous system., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
48. Doxycycline Inhibition of a Pseudotyped Virus Transduction Does Not Translate to Inhibition of SARS-CoV-2 Infectivity.
- Author
-
Diomede L, Baroni S, De Luigi A, Piotti A, Lucchetti J, Fracasso C, Russo L, Bonaldo V, Panini N, Filippini F, Fiordaliso F, Corbelli A, Beeg M, Pizzato M, Caccuri F, Gobbi M, Biasini E, Caruso A, and Salmona M
- Subjects
- Angiotensin-Converting Enzyme 2 metabolism, Animals, COVID-19 metabolism, Cell Cycle, Chlorocebus aethiops, Doxycycline pharmacology, HEK293 Cells, Humans, Protein Binding, SARS-CoV-2 ultrastructure, Spike Glycoprotein, Coronavirus, Transduction, Genetic, Vero Cells, COVID-19 virology, Host-Pathogen Interactions, SARS-CoV-2 drug effects, SARS-CoV-2 physiology, Virus Physiological Phenomena drug effects, Virus Replication drug effects
- Abstract
The rapid spread of the pandemic caused by the SARS-CoV-2 virus has created an unusual situation, with rapid searches for compounds to interfere with the biological processes exploited by the virus. Doxycycline, with its pleiotropic effects, including anti-viral activity, has been proposed as a therapeutic candidate for COVID-19 and about twenty clinical trials have started since the beginning of the pandemic. To gain information on the activity of doxycycline against SARS-CoV-2 infection and clarify some of the conflicting clinical data published, we designed in vitro binding tests and infection studies with a pseudotyped virus expressing the spike protein, as well as a clinically isolated SARS-CoV-2 strain. Doxycycline inhibited the transduction of the pseudotyped virus in Vero E6 and HEK-293 T cells stably expressing human receptor angiotensin-converting enzyme 2 but did not affect the entry and replication of SARS-CoV-2. Although this conclusion is apparently disappointing, it is paradigmatic of an experimental approach aimed at developing an integrated multidisciplinary platform which can shed light on the mechanisms of action of potential anti-COVID-19 compounds. To avoid wasting precious time and resources, we believe very stringent experimental criteria are needed in the preclinical phase, including infectivity studies with clinically isolated SARS-CoV-2, before moving on to (futile) clinical trials.
- Published
- 2021
- Full Text
- View/download PDF
49. Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis.
- Author
-
Pasetto L, Callegaro S, Corbelli A, Fiordaliso F, Ferrara D, Brunelli L, Sestito G, Pastorelli R, Bianchi E, Cretich M, Chiari M, Potrich C, Moglia C, Corbo M, Sorarù G, Lunetta C, Calvo A, Chiò A, Mora G, Pennuto M, Quattrone A, Rinaldi F, D'Agostino VG, Basso M, and Bonetto V
- Subjects
- Adult, Aged, Aged, 80 and over, Animals, Female, Humans, Machine Learning, Male, Mice, Microscopy, Electron, Transmission, Middle Aged, Proteomics, Amyotrophic Lateral Sclerosis blood, Amyotrophic Lateral Sclerosis diagnosis, Biomarkers blood, Extracellular Vesicles metabolism, Extracellular Vesicles ultrastructure
- Abstract
Background: Amyotrophic lateral sclerosis (ALS) is a multifactorial, multisystem motor neuron disease for which currently there is no effective treatment. There is an urgent need to identify biomarkers to tackle the disease's complexity and help in early diagnosis, prognosis, and therapy. Extracellular vesicles (EVs) are nanostructures released by any cell type into body fluids. Their biophysical and biochemical characteristics vary with the parent cell's physiological and pathological state and make them an attractive source of multidimensional data for patient classification and stratification., Methods: We analyzed plasma-derived EVs of ALS patients (n = 106) and controls (n = 96), and SOD1
G93A and TDP-43Q331K mouse models of ALS. We purified plasma EVs by nickel-based isolation, characterized their EV size distribution and morphology respectively by nanotracking analysis and transmission electron microscopy, and analyzed EV markers and protein cargos by Western blot and proteomics. We used machine learning techniques to predict diagnosis and prognosis., Results: Our procedure resulted in high-yield isolation of intact and polydisperse plasma EVs, with minimal lipoprotein contamination. EVs in the plasma of ALS patients and the two mouse models of ALS had a distinctive size distribution and lower HSP90 levels compared to the controls. In terms of disease progression, the levels of cyclophilin A with the EV size distribution distinguished fast and slow disease progressors, a possibly new means for patient stratification. Immuno-electron microscopy also suggested that phosphorylated TDP-43 is not an intravesicular cargo of plasma-derived EVs., Conclusions: Our analysis unmasked features in plasma EVs of ALS patients with potential straightforward clinical application. We conceived an innovative mathematical model based on machine learning which, by integrating EV size distribution data with protein cargoes, gave very high prediction rates for disease diagnosis and prognosis., (© 2021. The Author(s).)- Published
- 2021
- Full Text
- View/download PDF
50. Advanced lung cancer inflammation index and its prognostic value in HPV-negative head and neck squamous cell carcinoma: a multicentre study.
- Author
-
Gaudioso P, Borsetto D, Tirelli G, Tofanelli M, Cragnolini F, Menegaldo A, Fabbris C, Molteni G, Marchioni D, Nicolai P, Bossi P, Ciorba A, Pelucchi S, Bianchini C, Mauramati S, Benazzo M, Giacomarra V, Di Carlo R, Sethi M, Polesel J, Fussey J, and Boscolo-Rizzo P
- Subjects
- Aged, Female, Humans, Lung Neoplasms pathology, Male, Middle Aged, Pneumonia pathology, Prognosis, Progression-Free Survival, Retrospective Studies, Lung Neoplasms complications, Lung Neoplasms secondary, Pneumonia complications, Squamous Cell Carcinoma of Head and Neck complications
- Abstract
Purpose: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment., Methods: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM)., Results: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51-6.90 for PFS and HR 3.41, CI 1.47-7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31-4.51 for PFS and HR = 2.40, 95% CI: 1.19-4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23-5.10 for PFS and HR = 2.60, 95% CI: 1.19-5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01-13.73) and death (HR = 5.68, 95% CI: 1.92-16.79) than low ALI and low PNI considered alone., Conclusions: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC.
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.