4,914 results on '"Molteni, R"'
Search Results
2. OP0073 UNRAVELING PATHOPHYSIOLOGY AND HEMATOPOIESIS OF VEXAS SYNDROME BY MULTI-OMICS ANALYSIS AND TARGETED GENE EDITING
- Author
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Campochiaro, C., primary, Molteni, R., additional, Pacini, G., additional, Fiumara, M., additional, Tomelleri, A., additional, Diral, E., additional, Stefanoni, D., additional, Varesi, A., additional, Weber, A., additional, Alfieri, R., additional, Albano, L., additional, Panigada, M., additional, Cantoni, E., additional, Canarutto, D., additional, Bassoricci, L., additional, Quaranta, P., additional, ’alessandro, A. D, additional, Matucci-Cerinic, M., additional, DI Micco, R., additional, Aiuti, A., additional, Ciceri, F., additional, Merelli, I., additional, Dagna, L., additional, Scala, S., additional, Cenci, S., additional, Naldini, L., additional, Ferrari, S., additional, and Cavalli, G., additional
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- 2024
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3. Activity-based anorexia (ABA) model: Effects on brain neuroinflammation, redox balance and neuroplasticity during the acute phase.
- Author
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Spero V, Scherma M, D'Amelio S, Collu R, Dedoni S, Camoglio C, Siddi C, Fratta W, Molteni R, and Fadda P
- Abstract
Several evidences suggest that immuno-inflammatory responses are involved in the pathogenesis of anorexia nervosa (AN). Herein we investigate the possible alteration of key mediators of inflammation, redox balance, and neuroplasticity in the brain of rats showing an anorexic-like phenotype. We modeled AN in adolescent female rats using the activity-based anorexia (ABA) paradigm and measured gene expression levels of targets of interest in the prefrontal cortex (PFC) and dorsal hippocampus (DH). We observed reduced mRNA levels of pro-inflammatory cytokines IL-1β and TNF-α, the inflammasome NLRP3, and the microglial marker CD11b in both PFC and DH of ABA animals. Conversely, the mRNA of IL-6, which acts as both a pro-inflammatory and anti-inflammatory cytokine, was increased. Moreover, we observed an overall upregulation of different antioxidant enzymes in PFC, while their profile was not affected or opposite in the DH, with the exception of MT1α. Interestingly, ABA animals showed elevated levels of the neuroplasticity marker BDNF in both PFC and DH. Our data indicate that ABA induction is associated with anatomical-specific cerebral alteration of mediators of neuroinflammation, oxidative balance and neuroplasticity. Although more research should be conducted, these results add important information about the role of these systems in the complex AN etiopathogenesis., 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 Elsevier Ltd. All rights reserved.)
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- 2024
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4. Shadows of quantum machine learning.
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Jerbi S, Gyurik C, Marshall SC, Molteni R, and Dunjko V
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Quantum machine learning is often highlighted as one of the most promising practical applications for which quantum computers could provide a computational advantage. However, a major obstacle to the widespread use of quantum machine learning models in practice is that these models, even once trained, still require access to a quantum computer in order to be evaluated on new data. To solve this issue, we introduce a class of quantum models where quantum resources are only required during training, while the deployment of the trained model is classical. Specifically, the training phase of our models ends with the generation of a 'shadow model' from which the classical deployment becomes possible. We prove that: (i) this class of models is universal for classically-deployed quantum machine learning; (ii) it does have restricted learning capacities compared to 'fully quantum' models, but nonetheless (iii) it achieves a provable learning advantage over fully classical learners, contingent on widely believed assumptions in complexity theory. These results provide compelling evidence that quantum machine learning can confer learning advantages across a substantially broader range of scenarios, where quantum computers are exclusively employed during the training phase. By enabling classical deployment, our approach facilitates the implementation of quantum machine learning models in various practical contexts., (© 2024. The Author(s).)
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- 2024
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5. TENT5C/FAM46C modulation in vivo reveals a trade-off between antibody secretion and tumor growth in multiple myeloma.
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Resnati M, Pennacchio S, Viviani L, Perini T, Materozzi M, Orfanelli U, Bordini J, Molteni R, Nuvolone M, Da Vià M, Lazzaroni F, Bolli N, Cenci S, and Milan E
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- Humans, Animals, Mice, Multiple Myeloma pathology, Multiple Myeloma immunology, Multiple Myeloma metabolism
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- 2024
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6. A novel chemically defined medium for the biotechnological and biomedical exploitation of the cell factory Leishmania tarentolae.
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Cattaneo GM, Varotto-Boccazzi I, Molteni R, Ronchetti F, Gabrieli P, Mendoza-Roldan JA, Otranto D, Montomoli E, Bandi C, and Epis S
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- Biotechnology methods, Cell Culture Techniques methods, Animals, Leishmania genetics, Leishmania metabolism, Recombinant Proteins genetics, Recombinant Proteins metabolism, Culture Media chemistry
- Abstract
The development of media for cell culture is a major issue in the biopharmaceutical industry, for the production of therapeutics, immune-modulating molecules and protein antigens. Chemically defined media offer several advantages, as they are free of animal-derived components and guarantee high purity and a consistency in their composition. Microorganisms of the genus Leishmania represent a promising cellular platform for production of recombinant proteins, but their maintenance requires supplements of animal origin, such as hemin and fetal bovine serum. In the present study, three chemically defined media were assayed for culturing Leishmania tarentolae, using both a wild-type strain and a strain engineered to produce a viral antigen. Among the three media, Schneider's Drosophila Medium supplemented with Horseradish Peroxidase proved to be effective for the maintenance of L. tarentolae promastigotes, also allowing the heterologous protein production by the engineered strain. Finally, the engineered strain was maintained in culture up to the 12th week without antibiotic, revealing its capability to produce the recombinant protein in the absence of selective pressure., (© 2024. The Author(s).)
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- 2024
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7. New Findings on the Crystal Polymorphism of Imepitoin.
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Bruni G, Capsoni D, Pellegrini A, Altomare A, Coduri M, Ferrara C, Galinetto P, and Molteni R
- Abstract
Scientific and industrial reasons dictate the study of the solid state of imepitoin, a highly safe and tolerable anticonvulsant drug used in the therapy of epileptic dogs that was approved in the Europe Union in 2013. Our investigations allowed us to discover the existence of a new polymorph of imepitoin, which finds itself in a monotropic relationship with the crystalline form (polymorph I) already known and present on the market. This form (polymorph II), obtained by crystallization from xylene, remains metastable under ambient conditions for at least 1 year. Both solid forms were characterized by thermal (DSC and TGA), spectroscopic (FT-IR and Raman), microscopic (SEM and HSM), and diffractometric techniques. The thermodynamic relationship between the two polymorphs (monotropic) is such that it is not possible to study the melting of polymorph II, not even by adopting appropriate experimental strategies. Our measurements highlighted that the melting peak of imepitoin actually also includes an onset of melt decomposition. The ab initio structure solution, obtained from synchrotron X-ray powder diffraction data collected at room temperature, allowed us to determine the crystal structure of the new polymorph (II). It crystallizes in the monoclinic crystal structure, P2
1 / c space group (#14), with a = 14.8687(6) Å, b = 7.2434(2) Å, c = 12.5592(4) Å, β = 107.5586(8)°, V = 1289.61(8) Å3, and Z = 4.- Published
- 2024
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8. Myelomonocytic cells in giant cell arteritis activate trained immunity programs sustaining inflammation and cytokine production
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Cantoni, E, Merelli, I, Stefanoni, D, Tomelleri, A, Campochiaro, C, Giordano, V, Panigada, M, Baldissera, E, Merlo Pich, L, Natoli, V, Ziogas, A, Domínguez-Andrés, J, De Luca, G, Mazza, D, Zambrano, S, Gnani, D, Ferrarini, M, Ferrero, E, Agresti, A, Vergani, B, Leone, B, Cenci, S, Ravelli, A, Matucci-Cerinic, M, D'Alessandro, A, Joosten, L, Dagna, L, Netea, M, Molteni, R, Cavalli, G, Cantoni, Eleonora, Merelli, Ivan, Stefanoni, Davide, Tomelleri, Alessandro, Campochiaro, Corrado, Giordano, Vito, Panigada, Maddalena, Baldissera, Elena M, Merlo Pich, Laura, Natoli, Valentina, Ziogas, Athanasios, Domínguez-Andrés, Jorge, De Luca, Giacomo, Mazza, Davide, Zambrano, Samuel, Gnani, Daniela, Ferrarini, Marina, Ferrero, Elisabetta, Agresti, Alessandra, Vergani, Barbara, Leone, Biagio Eugenio, Cenci, Simone, Ravelli, Angelo, Matucci-Cerinic, Marco, D'Alessandro, Angelo, Joosten, Leo A B, Dagna, Lorenzo, Netea, Mihai G, Molteni, Raffaella, Cavalli, Giulio, Cantoni, E, Merelli, I, Stefanoni, D, Tomelleri, A, Campochiaro, C, Giordano, V, Panigada, M, Baldissera, E, Merlo Pich, L, Natoli, V, Ziogas, A, Domínguez-Andrés, J, De Luca, G, Mazza, D, Zambrano, S, Gnani, D, Ferrarini, M, Ferrero, E, Agresti, A, Vergani, B, Leone, B, Cenci, S, Ravelli, A, Matucci-Cerinic, M, D'Alessandro, A, Joosten, L, Dagna, L, Netea, M, Molteni, R, Cavalli, G, Cantoni, Eleonora, Merelli, Ivan, Stefanoni, Davide, Tomelleri, Alessandro, Campochiaro, Corrado, Giordano, Vito, Panigada, Maddalena, Baldissera, Elena M, Merlo Pich, Laura, Natoli, Valentina, Ziogas, Athanasios, Domínguez-Andrés, Jorge, De Luca, Giacomo, Mazza, Davide, Zambrano, Samuel, Gnani, Daniela, Ferrarini, Marina, Ferrero, Elisabetta, Agresti, Alessandra, Vergani, Barbara, Leone, Biagio Eugenio, Cenci, Simone, Ravelli, Angelo, Matucci-Cerinic, Marco, D'Alessandro, Angelo, Joosten, Leo A B, Dagna, Lorenzo, Netea, Mihai G, Molteni, Raffaella, and Cavalli, Giulio
- Abstract
Objective: Trained immunity (TI) is a de facto memory program of innate immune cells, characterized by immunometabolic and epigenetic changes sustaining enhanced production of cytokines. TI evolved as a protective mechanism against infections; however, inappropriate activation can cause detrimental inflammation and might be implicated in the pathogenesis of chronic inflammatory diseases. In this study, we investigated the role of TI in the pathogenesis of giant cell arteritis (GCA), a large-vessel vasculitis characterized by aberrant macrophage activation and excess cytokine production. Methods: Monocytes from GCA patients and from age- and sex-matched healthy donors were subjected to polyfunctional studies, including cytokine production assays at baseline and following stimulation, intracellular metabolomics, chromatin immunoprecipitation-qPCR, and combined ATAC/RNA sequencing. Immunometabolic activation (i.e. glycolysis) was assessed in inflamed vessels of GCA patients with FDG-PET and immunohistochemistry (IHC), and the role of this pathway in sustaining cytokine production was confirmed with selective pharmacologic inhibition in GCA monocytes. Results: GCA monocytes exhibited hallmark molecular features of TI. Specifically, these included enhanced IL-6 production upon stimulation, typical immunometabolic changes (e.g. increased glycolysis and glutaminolysis) and epigenetic changes promoting enhanced transcription of genes governing pro-inflammatory activation. Immunometabolic changes of TI (i.e. glycolysis) were a feature of myelomonocytic cells in GCA lesions and were required for enhanced cytokine production. Conclusions: Myelomonocytic cells in GCA activate TI programs sustaining enhanced inflammatory activation with excess cytokine production.
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- 2023
9. The Natural Protoalkaloid Methyl-2-Amino-3-Methoxybenzoate (MAM) Alleviates Positive as well as Cognitive Symptoms in Rat and Mouse Schizophrenia Models.
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Bright Y, Maas DA, Verheij MMM, Paladini MS, Amatdjais-Groenen HIV, Molteni R, Riva MA, Martens GJM, and Homberg JR
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- Rats, Mice, Animals, Apomorphine pharmacology, Apomorphine therapeutic use, Hydroxybenzoate Ethers therapeutic use, Disease Models, Animal, Cognition, Antipsychotic Agents pharmacology, Antipsychotic Agents therapeutic use, Schizophrenia chemically induced, Schizophrenia drug therapy
- Abstract
The development of new antipsychotics with pro-cognitive properties and less side effects represents a priority in schizophrenia drug research. In this study, we present for the first time a preclinical exploration of the effects of the promising natural atypical antipsychotic Methyl-2-Amino-3- Methoxybenzoate (MAM), a brain-penetrable protoalkaloid from the seed of the plant Nigella damascena. Using animal models related to hyperdopaminergic activity, namely the pharmacogenetic apomorphine (D2/D1 receptor agonist)-susceptible (APO-SUS) rat model and pharmacologically induced mouse and rat models of schizophrenia, we found that MAM reduced gnawing stereotypy and climbing behaviours induced by dopaminergic agents. This predicts antipsychotic activity. In line, MAM antagonized apomorphine-induced c-Fos and NPAS4 mRNA levels in post-mortem brain nucleus accumbens and dorsolateral striatum of APO-SUS rats. Furthermore, phencyclidine (PCP, an NMDA receptor antagonist) and 2,5-Dimethoxy-4-iodoamphetamine (DOI, a 5HT2A/2C receptor agonist) induced prepulse inhibition deficits, reflecting the positive symptoms of schizophrenia, which were rescued by treatment with MAM and atypical antipsychotics alike. Post-mortem brain immunostaining revealed that MAM blocked the strong activation of both PCP- and DOI-induced c-Fos immunoreactivity in a number of cortical areas. Finally, during a 28-day subchronic treatment regime, MAM did not induce weight gain, hyperglycemia, hyperlipidemia or hepato- and nephrotoxic effects, side effects known to be induced by atypical antipsychotics. MAM also did not show any cataleptic effects. In conclusion, its brain penetrability, the apparent absence of preclinical side effects, and its ability to antagonize positive and cognitive symptoms associated with schizophrenia make MAM an exciting new antipsychotic drug that deserves clinical testing., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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10. POS0492 MALADAPTIVE ACTIVATION OF TRAINED IMMUNITY IN THE PATHOGENESIS AND TREATMENT OF GIANT CELL ARTERITIS
- Author
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Cantoni, E., primary, Merelli, I., additional, Stefanoni, D., additional, Tomelleri, A., additional, Campochiaro, C., additional, Baldissera, E., additional, Dominguez Andres, J., additional, Matucci-Cerinic, M., additional, D’alessandro, A., additional, Dagna, L., additional, Netea, M., additional, Molteni, R., additional, and Cavalli, G., additional
- Published
- 2022
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11. Myelomonocytic cells in giant cell arteritis activate trained immunity programs sustaining inflammation and cytokine production.
- Author
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Cantoni E, Merelli I, Stefanoni D, Tomelleri A, Campochiaro C, Giordano V, Panigada M, Baldissera EM, Merlo Pich L, Natoli V, Ziogas A, Domínguez-Andrés J, De Luca G, Mazza D, Zambrano S, Gnani D, Ferrarini M, Ferrero E, Agresti A, Vergani B, Leone BE, Cenci S, Ravelli A, Matucci-Cerinic M, D'Alessandro A, Joosten LAB, Dagna L, Netea MG, Molteni R, and Cavalli G
- Subjects
- Humans, Monocytes metabolism, Trained Immunity, Inflammation, Cytokines, Giant Cell Arteritis pathology
- Abstract
Objective: Trained immunity (TI) is a de facto memory program of innate immune cells, characterized by immunometabolic and epigenetic changes sustaining enhanced production of cytokines. TI evolved as a protective mechanism against infections; however, inappropriate activation can cause detrimental inflammation and might be implicated in the pathogenesis of chronic inflammatory diseases. In this study, we investigated the role of TI in the pathogenesis of giant cell arteritis (GCA), a large-vessel vasculitis characterized by aberrant macrophage activation and excess cytokine production., Methods: Monocytes from GCA patients and from age- and sex-matched healthy donors were subjected to polyfunctional studies, including cytokine production assays at baseline and following stimulation, intracellular metabolomics, chromatin immunoprecipitation-qPCR, and combined ATAC/RNA sequencing. Immunometabolic activation (i.e. glycolysis) was assessed in inflamed vessels of GCA patients with FDG-PET and immunohistochemistry (IHC), and the role of this pathway in sustaining cytokine production was confirmed with selective pharmacologic inhibition in GCA monocytes., Results: GCA monocytes exhibited hallmark molecular features of TI. Specifically, these included enhanced IL-6 production upon stimulation, typical immunometabolic changes (e.g. increased glycolysis and glutaminolysis) and epigenetic changes promoting enhanced transcription of genes governing pro-inflammatory activation. Immunometabolic changes of TI (i.e. glycolysis) were a feature of myelomonocytic cells in GCA lesions and were required for enhanced cytokine production., Conclusions: Myelomonocytic cells in GCA activate TI programs sustaining enhanced inflammatory activation with excess cytokine production., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2023
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12. Immunometabolic activation of macrophages leads to cytokine production in the pathogenesis of KRAS-mutated histiocytosis
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Ferrero, E, Villa, A, Stefanoni, D, Nemkov, T, D'Alessandro, A, Tengesdal, I, Belloni, D, Molteni, R, Vergani, B, De Luca, G, Grassini, G, Giulia Cangi, M, Dagna, L, Doglioni, C, Cavalli, G, Ferrarini, M, Elisabetta Ferrero, Antonello Villa, Davide Stefanoni, Travis Nemkov, Angelo D'Alessandro, Isak Tengesdal, Daniela Belloni, Raffaella Molteni, Barbara Vergani, Giacomo De Luca, Greta Grassini, Maria Giulia Cangi, Lorenzo Dagna, Claudio Doglioni, Giulio Cavalli, Marina Ferrarini, Ferrero, E, Villa, A, Stefanoni, D, Nemkov, T, D'Alessandro, A, Tengesdal, I, Belloni, D, Molteni, R, Vergani, B, De Luca, G, Grassini, G, Giulia Cangi, M, Dagna, L, Doglioni, C, Cavalli, G, Ferrarini, M, Elisabetta Ferrero, Antonello Villa, Davide Stefanoni, Travis Nemkov, Angelo D'Alessandro, Isak Tengesdal, Daniela Belloni, Raffaella Molteni, Barbara Vergani, Giacomo De Luca, Greta Grassini, Maria Giulia Cangi, Lorenzo Dagna, Claudio Doglioni, Giulio Cavalli, and Marina Ferrarini
- Published
- 2022
13. Behavioural and molecular effects of the antipsychotic drug blonanserin in the chronic mild stress model
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Riva, M.A., Begni, V., Spero, V., Molteni, R., and Papp, M.
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- 2022
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14. Oral and Maxillofacial Radiology
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Molteni, R., primary
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- 2014
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15. Oncogene-induced maladaptive activation of trained immunity in the pathogenesis and treatment of Erdheim-Chester disease.
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Molteni, R., Biavasco, R., Stefanoni, D., Nemkov, T., Dominguez Andres, J., Arts, R.J.W., Merelli, I., Mazza, D., Zambrano, S., Panigada, M., Cantoni, E., Tengesdal, I.W., Maksud, P., Piras, F., Cesana, D., Cassina, L., Distefano, G., Loffreda, A., Gnani, D., Luca, G. De, Tomelleri, A., Campochiaro, C., Joosten, L.A.B., Dinarello, C.A., Kajaste-Rudnitski, A., Haroche, J., Cardaci, S., Cenci, S., Dagna, L., Doglioni, C., Ferrarini, M., Ferrero, E., Boletta, A., d'Alessandro, A., Montini, E., Netea, M.G., Cavalli, G.C., Molteni, R., Biavasco, R., Stefanoni, D., Nemkov, T., Dominguez Andres, J., Arts, R.J.W., Merelli, I., Mazza, D., Zambrano, S., Panigada, M., Cantoni, E., Tengesdal, I.W., Maksud, P., Piras, F., Cesana, D., Cassina, L., Distefano, G., Loffreda, A., Gnani, D., Luca, G. De, Tomelleri, A., Campochiaro, C., Joosten, L.A.B., Dinarello, C.A., Kajaste-Rudnitski, A., Haroche, J., Cardaci, S., Cenci, S., Dagna, L., Doglioni, C., Ferrarini, M., Ferrero, E., Boletta, A., d'Alessandro, A., Montini, E., Netea, M.G., and Cavalli, G.C.
- Abstract
Item does not contain fulltext, Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.
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- 2021
16. Developmental and stress-related changes of neurotrophic factor gene expression in an animal model of schizophrenia
- Author
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Molteni, R, Lipska, B K, Weinberger, D R, Racagni, G, and Riva, M A
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- 2001
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17. Study of electron beam irradiation effects on 2,4,6-trichloroanisole as a contaminant of cork by gas chromatography-mass spectrometry
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Careri, M., Mazzoleni, V., Musci, M., and Molteni, R.
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- 2001
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18. Effects of electron beam irradiation on cork volatile compounds by gas chromatography-mass spectrometry
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Careri, M., Mazzoleni, V., Musci, M., and Molteni, R.
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- 1999
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19. Involvement of the IL-6 Signaling Pathway in the Anti-Anhedonic Effect of the Antidepressant Agomelatine in the Chronic Mild Stress Model of Depression.
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Rossetti AC, Paladini MS, Brüning CA, Spero V, Cattaneo MG, Racagni G, Papp M, Riva MA, and Molteni R
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- Animals, Rats, Male, Depression drug therapy, Depression etiology, Depression metabolism, Rats, Wistar, Antidepressive Agents pharmacology, Antidepressive Agents therapeutic use, Signal Transduction, Inflammation Mediators metabolism, Suppressor of Cytokine Signaling Proteins metabolism, Sucrose, Interleukin-6 genetics, Interleukin-6 metabolism, Depressive Disorder, Major drug therapy
- Abstract
Neuroinflammation has emerged as an important factor in the molecular underpinnings of major depressive disorder (MDD) pathophysiology and in the mechanism of action of antidepressants. Among the inflammatory mediators dysregulated in depressed patients, interleukin (IL)-6 has recently been proposed to play a crucial role. IL-6 activates a signaling pathway comprising the JAK/STAT proteins and characterized by a specific negative feedback loop exerted by the cytoplasmic protein suppressor of cytokine signalling-3 (SOCS3). On these bases, here, we explored the potential involvement of IL-6 signaling in the ability of the antidepressant drug agomelatine to normalize the anhedonic-like phenotype induced in the rat by chronic stress exposure. To this aim, adult male Wistar rats were subjected to the chronic mild stress (CMS) paradigm and chronically treated with vehicle or agomelatine. The behavioral evaluation was assessed by the sucrose consumption test, whereas molecular analyses were performed in the prefrontal cortex. We found that CMS was able to stimulate IL-6 production and signaling, including SOCS3 gene and protein expression, but the SOCS3-mediated feedback-loop inhibition failed to suppress the IL-6 cascade in stressed animals. Conversely, agomelatine treatment normalized the stress-induced decrease in sucrose consumption and restored the negative modulation of the IL-6 signaling via SOCS3 expression and activity. Our results provide additional information about the pleiotropic mechanisms that contribute to agomelatine's therapeutic effects.
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- 2022
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20. Altered responsiveness of the antioxidant system in chronically stressed animals: modulation by chronic lurasidone treatment.
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Spero V, Paladini MS, Brivio P, Riva MA, Calabrese F, and Molteni R
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- Animals, Antioxidants pharmacology, Brain metabolism, Brain-Derived Neurotrophic Factor metabolism, Humans, Male, Rats, Antipsychotic Agents pharmacology, Antipsychotic Agents therapeutic use, Lurasidone Hydrochloride pharmacology
- Abstract
Rationale: Although the occurrence of stressful events is very common during life, their impact may be different depending on the experience severity and duration. Specifically, acute challenges may trigger adaptive responses and even improve the individual's performance. However, such a physiological positive coping can only take place if the underlying molecular mechanisms are properly functioning. Indeed, if these systems are compromised by genetic factors or previous adverse conditions, the response set in motion by an acute challenge may be maladaptive and even cause the insurgence or the relapse of stress-related psychiatric disorders., Objectives: On these bases, we evaluated in the rat brain the role of the antioxidant component of the redox machinery on the acute stress responsiveness and its modulation by potential detrimental or beneficial events., Methods: The expression of several antioxidant enzymes was assessed in different brain areas of adult male rats exposed to acute stress 3 weeks after a chronic immobilization paradigm with or without a concomitant treatment with the antipsychotic lurasidone., Results: The acute challenge was able to trigger a marked antioxidant response that, despite the washout period, was impaired by the previous adverse experience and restored by lurasidone in an anatomical-specific manner., Conclusions: We found that a working antioxidant machinery takes part in acute stress response and may be differentially affected by other experiences. Given the essential role of stress responsiveness in almost every life process, the identification of the underlying mechanisms and their potential pharmacological modulation add further translational value to our data., (© 2022. The Author(s).)
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- 2022
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21. AB0052 ROLE OF TRAINED IMMUNITY AND IMMUNOMETABOLISM IN THE PATHOGENESIS OF ERDHEIM-CHESTER DISEASE
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Biavasco, R., primary, Molteni, R., additional, Stefanoni, D., additional, Ferrarini, M., additional, Ferrero, E., additional, Cenci, S., additional, Cardaci, S., additional, Boletta, A., additional, Cassina, L., additional, Di Stefano, G., additional, Dominguez Andres, J., additional, Doglioni, C., additional, Nemkov, T., additional, Merelli, I., additional, D’alessandro, A., additional, Montini, E., additional, Netea, M., additional, Dagna, L., additional, and Cavalli, G., additional
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- 2020
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22. P.333 Multimodal neuroplastic mechanisms of lurasidone treatment in the chronic mild stress model
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Calabrese, F., primary, Brivio, P., additional, Sbrini, G., additional, Paladini, M.S., additional, Spero, V., additional, Papp, M., additional, Molteni, R., additional, and Riva, M.A., additional
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- 2019
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23. P.404 Neuroplastic changes following chronic treatment with antipsychotic blonanserin in rats: Implications for schizophrenia
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Marchisella, F., primary, Paladini, M.S., additional, Begni, V., additional, Brivio, P., additional, Spero, V., additional, Calabrese, F., additional, Molteni, R., additional, and Riva, M.A., additional
- Published
- 2019
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24. Chronic fluoxetine administration inhibits extracellular signal-regulated kinase 1/2 phosphorylation in rat brain
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Fumagalli, F., Molteni, R., Calabrese, F., Frasca, A., Racagni, G., and Riva, M. A.
- Published
- 2005
25. Prenatal Stress Impairs Spinal Cord Oligodendrocyte Maturation via BDNF Signaling in the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis.
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Paladini MS, Marangon D, Rossetti AC, Guidi A, Coppolino GT, Negri C, Spero V, Abbracchio MP, Lecca D, and Molteni R
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- Animals, Brain-Derived Neurotrophic Factor metabolism, Female, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins metabolism, Oligodendroglia metabolism, Receptors, G-Protein-Coupled metabolism, Spinal Cord metabolism, Encephalomyelitis, Autoimmune, Experimental metabolism, Multiple Sclerosis metabolism
- Abstract
One of the most substantial and established environmental risk factors for neurological and psychiatric disorders is stress exposure, whose detrimental consequences hinge on several variables including time. In this regard the gestational period is known to present an intrinsic vulnerability to environmental insults and thus stressful events during pregnancy can lead to severe consequences on the offspring's brain development with long-term repercussions throughout adulthood. On this basis, we investigated the long-lasting impact of prenatal stress exposure on the susceptibility to the experimental autoimmune encephalomyelitis (EAE), a well-established murine model of multiple sclerosis. Although stress is considered a triggering factor for this chronic, progressive, autoimmune disease, little is known about the underlying mechanisms. To this end, EAE was induced by immunization with MOG35-55/CFA and pertussis toxin administration in adult female C57BL/6 mice born from control or stressed dams exposed to restraint stress during the last days of gestation. Our results demonstrate that gestational stress induces a marked increase in the severity of EAE symptoms in adulthood. Further, we highlight an altered maturation of oligodendrocytes in the spinal cord of prenatally stressed EAE mice, as indicated by the higher levels of GPR17, a marker of immature oligodendrocyte precursor cells. These behavioral and molecular alterations are paralleled by changes in the expression and signaling of the neurotrophin BDNF, an important mediator of neural plasticity that may contribute to stress-induced impaired remyelination. Since several already marketed drugs are able to modulate BDNF levels, these results pave the way to the possibility of repositioning these drugs in multiple sclerosis., (© 2020. The Author(s).)
- Published
- 2022
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26. Immunometabolic activation of macrophages leads to cytokine production in the pathogenesis of KRAS-mutated histiocytosis.
- Author
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Ferrero E, Villa A, Stefanoni D, Nemkov T, D'Alessandro A, Tengesdal I, Belloni D, Molteni R, Vergani B, De Luca G, Grassini G, Cangi MG, Dagna L, Doglioni C, Cavalli G, and Ferrarini M
- Subjects
- Cytokines metabolism, Gene Expression, Humans, Macrophages metabolism, Mutation, Histiocytosis genetics, Histiocytosis pathology, Proto-Oncogene Proteins p21(ras) genetics
- Published
- 2022
- Full Text
- View/download PDF
27. Chronic treatment with the antipsychotic drug blonanserin modulates the responsiveness to acute stress with anatomical selectivity.
- Author
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Marchisella F, Paladini MS, Guidi A, Begni V, Brivio P, Spero V, Calabrese F, Molteni R, and Riva MA
- Subjects
- Animals, Brain physiology, Drug Administration Schedule, Genes, Immediate-Early physiology, Male, Rats, Rats, Sprague-Dawley, Receptors, Dopamine metabolism, Schizophrenia drug therapy, Schizophrenia genetics, Stress, Psychological genetics, Stress, Psychological psychology, Antipsychotic Agents administration & dosage, Brain drug effects, Genes, Immediate-Early drug effects, Piperazines administration & dosage, Piperidines administration & dosage, Stress, Psychological drug therapy
- Abstract
Rationale: Patients diagnosed with schizophrenia typically receive life-long treatments with antipsychotic drugs (APDs). However, the impact of chronic APDs treatment on neuroplastic mechanisms in the brain remains largely elusive., Objective: Here, we focused on blonanserin, a second-generation antipsychotic (SGA) that acts as an antagonist at dopamine D2, D3, and serotonin 5-HT2A receptors, and represents an important tool for the treatment of schizophrenia., Methods: We used rats to investigate the ability of chronic treatment blonanserin to modulate the activity of brain structures relevant for schizophrenia, under baseline conditions or in response to an acute forced swim session (FSS). We measured the expression of different immediate early genes (IEGs), including c-Fos, Arc/Arg 3.1, Zif268 and Npas4., Results: Blonanserin per se produced limited changes in the expression of these genes under basal conditions, while, as expected, FSS produced a significant elevation of IEGs transcription in different brain regions. The response of blonanserin-treated rats to FSS show anatomical and gene-selective differences. Indeed, the upregulation of IEGs was greatly reduced in the striatum, a brain structure enriched in dopamine receptors, whereas the upregulation of some genes (Zif268, Npas4) was largely preserved in other regions, such as the prefrontal cortex and the ventral hippocampus., Conclusions: Taken together, our findings show that chronic exposure to blonanserin modulates selective IEGs with a specific anatomical profile. Moreover, the differential activation of specific brain regions under challenging conditions may contribute to specific clinical features of the drug.
- Published
- 2020
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28. Spatial ecology of crested porcupine in a metropolitan landscape.
- Author
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Mori E, Molteni R, Ancillotto L, Ficetola GF, and Falaschi M
- Abstract
Human settlements, including cities, may provide wildlife with new ecological niches, in terms of habitat types and food availability, thus requiring plasticity for adaptation. The crested porcupine Hystrix cristata is a habitat-generalist, large-sized rodent, also recorded in some suburban areas, but no information is available on its habitat use in metropolitan landscapes. Here, we assessed the land-use factors influencing the presence of crested porcupines in a metropolitan area of Central Italy. We collected data on the occurrence of crested porcupines from the metropolitan area of Rome, following an observer-oriented approach to record occurrences and retreive pseudo-absences. We then related the presence/absence of H. cristata to landscape composition. Occupancy models showed that cultivations and scrubland were positively related to porcupine presence, most likely as they provide food resources and shelter sites, respectively. Although the crested porcupine has been confirmed as a "generalist" species in terms of habitat selection, a strong preference for areas limiting the risk of being killed and providing enough food and shelter was observed. We therefore suggest that the crested porcupine may adapt to deeply modified landscapes such as large cities by selecting specific favourable land-use types., Competing Interests: Competing interestsAuthors declare that they have no competing interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)
- Published
- 2022
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29. BACHD rats expressing full-length mutant huntingtin exhibit differences in social behavior compared to wild-type littermates
- Author
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Manfré, G., Novati, Arianna, Faccini, Ilaria, Rossetti, Andrea C., Bosch, K.J., Molteni, R., Harst, J.E. van der, Nguyen, H.P., Homberg, J.R., Manfré, G., Novati, Arianna, Faccini, Ilaria, Rossetti, Andrea C., Bosch, K.J., Molteni, R., Harst, J.E. van der, Nguyen, H.P., and Homberg, J.R.
- Abstract
Contains fulltext : 189759.pdf (publisher's version ) (Open Access)
- Published
- 2018
30. International union of basic and clinical pharmacology CIV: The neurobiology of treatment-resistant depression: From antidepressant classifications to novel pharmacological targets
- Author
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Caraci, Filippo, Calabrese, Francesca, Molteni, R., Bartova, Lucie, Dold, Markus, Leggio, Gian Marco, Fabbri, Chiara, Mendlewicz, Julien, Racagni, Giorgio, Kasper, Siegfried S.F., Riva, Marco Andrea, Drago, Filippo, Caraci, Filippo, Calabrese, Francesca, Molteni, R., Bartova, Lucie, Dold, Markus, Leggio, Gian Marco, Fabbri, Chiara, Mendlewicz, Julien, Racagni, Giorgio, Kasper, Siegfried S.F., Riva, Marco Andrea, and Drago, Filippo
- Abstract
Major depressive disorder is one of the most prevalent and life-threatening forms of mental illnesses and a major cause of morbidity worldwide. Currently available antidepressants are effective for most patients, although around 30% are considered treatment resistant (TRD), a condition that is associated with a significant impairment of cognitive function and poor quality of life. In this respect, the identification of the molecularmechanisms contributing to TRD represents an essential step for the design of novel and more efficacious drugs able to modify the clinical course of this disorder and increase remission rates in clinical practice. New insights into the neurobiology of TRD have shed light on the role of a number of different mechanisms, including the glutamatergic system, immune/inflammatory systems, neurotrophin function, and epigenetics. Advances in drug discovery processes in TRD have also influenced the classification of antidepressant drugs and novel classifications are available, such as the neurosciencebased nomenclature that can incorporate such advances in drug development for TRD. This reviewaims to provide an up-to-date description of key mechanisms in TRD and describe current therapeutic strategies for TRD before examining novel approaches that may ultimately address important neurobiological mechanisms not targeted by currently available antidepressants. All in all, we suggest that drug targeting different neurobiological systems should be able to restore normal function but must also promote resilience to reduce the long-termvulnerability to recurrent depressive episodes., SCOPUS: re.j, info:eu-repo/semantics/published
- Published
- 2018
31. Oncogene-induced maladaptive activation of trained immunity in the pathogenesis and treatment of Erdheim-Chester disease.
- Author
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Molteni R, Biavasco R, Stefanoni D, Nemkov T, Domínguez-Andrés J, Arts RJ, Merelli I, Mazza D, Zambrano S, Panigada M, Cantoni E, Tengesdal IW, Maksud P, Piras F, Cesana D, Cassina L, Distefano G, Loffreda A, Gnani D, De Luca G, Tomelleri A, Campochiaro C, Joosten LAB, Dinarello CA, Kajaste-Rudnitski A, Haroche J, Cardaci S, Cenci S, Dagna L, Doglioni C, Ferrarini M, Ferrero E, Boletta A, D'Alessandro A, Montini E, Netea MG, and Cavalli G
- Subjects
- Cells, Cultured, Epigenesis, Genetic, Erdheim-Chester Disease immunology, Erdheim-Chester Disease pathology, Humans, Immunity, Inflammation immunology, Inflammation pathology, Macrophages immunology, Macrophages metabolism, Macrophages pathology, Oncogenes, Point Mutation, Proto-Oncogene Proteins B-raf immunology, Erdheim-Chester Disease genetics, Inflammation genetics, Proto-Oncogene Proteins B-raf genetics
- Abstract
Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation., (© 2021 by The American Society of Hematology.)
- Published
- 2021
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32. International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets
- Author
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Caraci, F., primary, Calabrese, F., additional, Molteni, R., additional, Bartova, L., additional, Dold, M., additional, Leggio, G. M., additional, Fabbri, C., additional, Mendlewicz, J., additional, Racagni, G., additional, Kasper, S., additional, Riva, M. A., additional, and Drago, F., additional
- Published
- 2018
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- View/download PDF
33. Depression-prone mice with reduced glucocorticoid receptor expression display an altered stress-dependent regulation of brain-derived neurotrophic factor and activity-regulated cytoskeleton-associated protein
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Molteni, R., Chourbaji, S., Brandwein, C., Racagni, G., Gass, P., and Riva, MA
- Subjects
Depression, Mental -- Genetic aspects ,Depression, Mental -- Care and treatment ,Gene expression -- Analysis ,Corticosteroids -- Health aspects ,Neuroplasticity -- Research ,Pharmaceuticals and cosmetics industries ,Psychology and mental health - Published
- 2010
34. The anti-inflammatory cytokine interleukin-37 is an inhibitor of trained immunity.
- Author
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Cavalli G, Tengesdal IW, Gresnigt M, Nemkov T, Arts RJW, Domínguez-Andrés J, Molteni R, Stefanoni D, Cantoni E, Cassina L, Giugliano S, Schraa K, Mills TS, Pietras EM, Eisenmensser EZ, Dagna L, Boletta A, D'Alessandro A, Joosten LAB, Netea MG, and Dinarello CA
- Subjects
- Animals, Candidiasis genetics, Candidiasis immunology, Candidiasis microbiology, Epigenesis, Genetic drug effects, Glycolysis drug effects, Glycolysis genetics, Host-Pathogen Interactions drug effects, Host-Pathogen Interactions immunology, Humans, Male, Mice, Inbred C57BL, Neutrophils drug effects, Neutrophils metabolism, Mice, Anti-Inflammatory Agents pharmacology, Immunity, Innate drug effects, Interleukin-1 pharmacology
- Abstract
Trained immunity (TI) is a de facto innate immune memory program induced in monocytes/macrophages by exposure to pathogens or vaccines, which evolved as protection against infections. TI is characterized by immunometabolic changes and histone post-translational modifications, which enhance production of pro-inflammatory cytokines. As aberrant activation of TI is implicated in inflammatory diseases, tight regulation is critical; however, the mechanisms responsible for this modulation remain elusive. Interleukin-37 (IL-37) is an anti-inflammatory cytokine that curbs inflammation and modulates metabolic pathways. In this study, we show that administration of recombinant IL-37 abrogates the protective effects of TI in vivo, as revealed by reduced host pro-inflammatory responses and survival to disseminated candidiasis. Mechanistically, IL-37 reverses the immunometabolic changes and histone post-translational modifications characteristic of TI in monocytes, thus suppressing cytokine production in response to infection. IL-37 thereby emerges as an inhibitor of TI and as a potential therapeutic target in immune-mediated pathologies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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35. The way we were (and how we got here): fifty years of technology changes in dental and maxillofacial radiology.
- Author
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Molteni R
- Subjects
- Cone-Beam Computed Tomography, Radiography, Technology, Radiography, Dental, Digital, Radiology
- Abstract
The history of the last 50 years (1970-2020) of technological changes and progresses for equipment and procedures in dental and maxillofacial radiology is related from the insider perspective of an industrial physicist and technologist who has been instrumental at innovating and developing medical equipment in different parts of the world. The onset and improvement of all major categories of dental and maxillofacial radiographic equipment is presented, from the standpoint of their practical acceptance and impact among common dentists and maxillofacial radiologists: X-ray sources and detectors for intraoral radiography, and panoramic systems, both film-based and digital (including photo-stimulated phosphor plates); and cone beam CT.
- Published
- 2021
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36. Behavioral and molecular effects of the antipsychotic drug blonanserin in the chronic mild stress model.
- Author
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Paladini MS, Spero V, Begni V, Marchisella F, Guidi A, Gruca P, Lason M, Litwa E, Papp M, Riva MA, and Molteni R
- Subjects
- Animals, Antipsychotic Agents pharmacology, Behavior, Animal drug effects, Brain drug effects, Brain metabolism, Cytoskeletal Proteins genetics, Disease Models, Animal, Male, Maze Learning drug effects, Nerve Tissue Proteins genetics, Oxidoreductases genetics, Piperazines pharmacology, Piperidines pharmacology, Rats, Wistar, Stress, Psychological genetics, Rats, Antipsychotic Agents therapeutic use, Piperazines therapeutic use, Piperidines therapeutic use, Stress, Psychological drug therapy
- Abstract
Psychiatric disorders represent a critical challenge to our society, given their high global prevalence, complex symptomatology, elusive etiology and the variable effectiveness of pharmacological therapies. Recently, there has been a shift in investigating and redefining these diseases by integrating behavioral observations and multilevel neurobiological measures. Accordingly, endophenotype-oriented studies are needed to develop new therapeutic strategies, with the idea of targeting shared symptoms instead of one defined disease. With these premises, here we investigated the therapeutic properties of chronic treatment with the second-generation antipsychotic blonanserin in counteracting the alterations caused by 7 weeks of Chronic Mild Stress (CMS) in the rat. CMS is a well-established preclinical model able to induce depressive and anxiety-like alterations, which are shared by different psychiatric disorders. Our results demonstrated that the antipsychotic treatment normalizes the CMS-induced emotionality deficits, an effect that may be due to its ability in modulating, within the prefrontal cortex, redox mechanisms, a molecular dysfunction associated with several psychiatric disorders. These evidences provide new insights into the therapeutic properties and potential use of blonanserin as well as in its mechanisms of action and provide further support for the role of oxidative stress in the pathophysiology of psychiatric disorders., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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37. Chronic stress exposure impairs GABAergic homeostasis in the hippocampus: restorative effect of the novel antipsychotic lurasidone
- Author
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Riva, M.A., primary, Rossetti, A., additional, Paladini, M.S., additional, Colombo, M., additional, and Molteni, R., additional
- Published
- 2017
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38. Investigating stress resilience and susceptibility: impact of lipopolysaccharide on the rat brain
- Author
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Paladini, M.S., primary, Rossetti, A.C., additional, Rubini, L., additional, Racagni, G., additional, Papp, M., additional, Riva, M.A., additional, and Molteni, R., additional
- Published
- 2017
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39. Autophagy in the Regulation of Tissue Differentiation and Homeostasis.
- Author
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Perrotta C, Cattaneo MG, Molteni R, and De Palma C
- Abstract
Autophagy is a constitutive pathway that allows the lysosomal degradation of damaged components. This conserved process is essential for metabolic plasticity and tissue homeostasis and is crucial for mammalian post-mitotic cells. Autophagy also controls stem cell fate and defective autophagy is involved in many pathophysiological processes. In this review, we focus on established and recent breakthroughs aimed at elucidating the impact of autophagy in differentiation and homeostasis maintenance of endothelium, muscle, immune system, and brain providing a suitable framework of the emerging results and highlighting the pivotal role of autophagic response in tissue functions, stem cell dynamics and differentiation rates., 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 © 2020 Perrotta, Cattaneo, Molteni and De Palma.)
- Published
- 2020
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40. Study of the different evaluation areas in the pesticide risk assessment process.
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Molteni R and Alonso-Prados JL
- Abstract
Approval of active substances and authorisation of plant protection products in the EU is made based on a strict risk assessment of the agronomic use of the plant protection products. Regulation 1107/2009 regulates the procedure in the EU with complex procedures involving many actors. 'The Farm to Fork strategy' and 'The Biodiversity for 2030 strategy', that are the heart of the 'European Green Deal', aiming to make food systems fair, healthy, environmentally friendly and put Europe's biodiversity on the path to recovery by 2030, for the benefit of people, climate and the planet. Therefore, 'The Farm to Fork strategy' and 'The Biodiversity for 2030 strategy' represents a challenge for the evaluation and authorisation of plant protection products in which the risk management will constitute a key element on the approval of active substances and authorisation of plant protection products. The aim of the work was to get knowledge of the large body of EU legislation and guidelines in the plant production products, identifying the most critical points of the pesticide evaluation in each of its areas, analysing the complexity and the interaction between these different areas. This study allowed to have a global and clearer vision of these procedures, with the focus on highlighting inconsistency and to propose speed up alternatives. Finally, this work will also facilitate not only the risk assessment but also the decision-making on the approval of active substances and the authorisation of plant protection products., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)
- Published
- 2020
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41. Bioavailability of curcumin in the rat frontal lobe and hippocampus after repeated administration of MERIVA®
- Author
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Dell'Agli, M, additional, Sangiovanni, E, additional, Risè, P, additional, Rossetti, AC, additional, Morazzoni, P, additional, Riva, A, additional, Racagni, G, additional, Sala, A, additional, and Molteni, R, additional
- Published
- 2016
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42. Flow chamber and uses thereof
- Author
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PARDI , RUGGERO, Molteni R, Dubini G, Bianchi E, Laganà K., Pardi, Ruggero, Molteni, R, Dubini, G, Bianchi, E, and Laganà, K.
- Subjects
Adhesion ,Extravasation ,Migration - Published
- 2013
43. The GIT/PIX complexes regulate the chemotactic response of rat basophilic leukemia cells
- Author
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GAVINA M, ZA L, MOLTENI R, PARDI R, DE CURTIS , IVANMATTEO, Gavina, M, Za, L, Molteni, R, Pardi, R, and DE CURTIS, Ivanmatteo
- Abstract
BACKGROUND INFORMATION:Cell motility entails the reorganization of the cytoskeleton and membrane trafficking for effective protrusion. The GIT-PIX protein complexes are involved in the regulation of cell motility and adhesion and in the endocytic traffic of members of the family of G-protein-coupled receptors. We have investigated the function of the endogenous GIT complexes in the regulation of cell motility stimulated by fMLP (formyl-Met-Leu-Phe) peptide, in a rat basophilic leukaemia RBL-2H3 cell line stably expressing an HA (haemagglutinin)-tagged receptor for the fMLP peptide.RESULTS:Our analysis shows that RBL cells stably transfected with the chemoattractant receptor expressed both GIT1-PIX and GIT2-PIX endogenous complexes. We have used silencing of the different members of the complex by small interfering RNAs to study the effects on a number of events linked to agonist-induced cell migration. We found that cell adhesion was not affected by depletion of any of the proteins of the GIT complex, whereas agonist-enhanced cell spreading was inhibited. Analysis of agonist-stimulated haptotactic cell migration indicated a specific positive effect of GIT1 depletion on trans-well migration. The internalization of the formyl-peptide receptor was also inhibited by depletion of GIT1 and GIT2. The effects of the GIT complexes on trafficking of the receptors was confirmed by an antibody-enhanced agonist-induced internalization assay, showing that depletion of PIX, GIT1 or GIT2 protein caused decreased perinuclear accumulation of internalized receptors.CONCLUSIONS:Our results show that endogenous GIT complexes are involved in the regulation of chemoattractant-induced cell motility and receptor trafficking, and support previous findings indicating an important function of the GIT complexes in the regulation of different G-protein-coupled receptors. Our results also indicate that endogenous GIT1 and GIT2 regulate distinct subsets of agonist-induced responses and suggest a possible functional link between the control of receptor trafficking and the regulation of cell motility by GIT proteins.
- Published
- 2010
44. Inhibitor of NF-kappa B kinases alpha and beta are both essential for high mobility group box 1-mediated chemotaxis
- Author
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Penzo M, Molteni R, Suda T, Samaniego S, Raucci A, Habiel DM, Miller F, Jiang HP, Li J, PARDI , RUGGERO, Palumbo R, Olivotto E, Kew RR, BIANCHI, MARCO EMILIO, Marcu K.B., Penzo, M, Molteni, R, Suda, T, Samaniego, S, Raucci, A, Habiel, Dm, Miller, F, Jiang, Hp, Li, J, Pardi, Ruggero, Palumbo, R, Olivotto, E, Kew, Rr, Bianchi, MARCO EMILIO, and Marcu, K. B.
- Abstract
Inhibitor of NF-kappaB kinases beta (IKKbeta) and alpha (IKKalpha) activate distinct NF-kappaB signaling modules. The IKKbeta/canonical NF-kappaB pathway rapidly responds to stress-like conditions, whereas the IKKalpha/noncanonical pathway controls adaptive immunity. Moreover, IKKalpha can attenuate IKKbeta-initiated inflammatory responses. High mobility group box 1 (HMGB1), a chromatin protein, is an extracellular signal of tissue damage-attracting cells in inflammation, tissue regeneration, and scar formation. We show that IKKalpha and IKKbeta are each critically important for HMGB1-elicited chemotaxis of fibroblasts, macrophages, and neutrophils in vitro and neutrophils in vivo. By time-lapse microscopy we dissected different parameters of the HMGB1 migration response and found that IKKalpha and IKKbeta are each essential to polarize cells toward HMGB1 and that each kinase also differentially affects cellular velocity in a time-dependent manner. In addition, HMGB1 modestly induces noncanonical IKKalpha-dependent p52 nuclear translocation and p52/RelB target gene expression. Akin to IKKalpha and IKKbeta, p52 and RelB are also required for HMGB1 chemotaxis, and p52 is essential for cellular orientation toward an HMGB1 gradient. RAGE, a ubiquitously expressed HMGB1 receptor, is required for HMGB1 chemotaxis. Moreover, IKKbeta, but not IKKalpha, is required for HMGB1 to induce RAGE mRNA, suggesting that RAGE is at least one IKKbeta target involved in HMGB1 migration responses, and in accord with these results enforced RAGE expression rescues the HMGB1 migration defect of IKKbeta, but not IKKalpha, null cells. Thus, proinflammatory HMGB1 chemotactic responses mechanistically require the differential collaboration of both IKK-dependent NF-kappaB signaling pathways.
- Published
- 2010
45. Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling.
- Author
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Brivio P, Sbrini G, Corsini G, Paladini MS, Racagni G, Molteni R, and Calabrese F
- Subjects
- Animals, Brain-Derived Neurotrophic Factor metabolism, Disease Models, Animal, Male, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases metabolism, Rats, Rats, Sprague-Dawley, Receptor, trkB genetics, Receptor, trkB metabolism, Signal Transduction, Stress, Psychological etiology, Stress, Psychological genetics, Brain-Derived Neurotrophic Factor genetics, Corticosterone metabolism, Prefrontal Cortex metabolism, Restraint, Physical psychology, Stress, Psychological metabolism
- Abstract
Depression is a recurrent disorder, with about 50% of patients experiencing relapse. Exposure to stressful events may have an adverse impact on the long-term course of the disorder and may alter the response to a subsequent stressor. Indeed, not all the systems impaired by stress may normalize during symptoms remission, facilitating the relapse to the pathology. Hence, we investigated the long-lasting effects of chronic restraint stress (CRS) and its influence on the modifications induced by the exposure to a second hit on brain-derived neurotrophic factor (BDNF) signaling in the prefrontal cortex (PFC). We exposed adult male Sprague Dawley rats to 4 weeks of CRS, we left them undisturbed for the subsequent 3 weeks, and then we exposed animals to one hour of acute restraint stress (ARS). We found that CRS influenced the release of corticosterone induced by ARS and inhibited the ability of ARS to activate mature BDNF, its receptor Tropomyosin receptor kinase B (TRKB), and their associated intracellular cascades: the TRKB-PI3K-AKT), the MEK-MAPK/ERK, and the Phospholipase C γ (PLCγ) pathways, positively modulated by ARS in non-stressed animals. These results suggest that CRS induces protracted and detrimental consequences that interfere with the ability of PFC to cope with a challenging situation.
- Published
- 2020
- Full Text
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46. Common Protective Strategies in Neurodegenerative Disease: Focusing on Risk Factors to Target the Cellular Redox System.
- Author
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Hrelia P, Sita G, Ziche M, Ristori E, Marino A, Cordaro M, Molteni R, Spero V, Malaguti M, Morroni F, and Hrelia S
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Humans, Middle Aged, Oxidation-Reduction, Risk Factors, Young Adult, Neurodegenerative Diseases therapy
- Abstract
Neurodegenerative disease is an umbrella term for different conditions which primarily affect the neurons in the human brain. In the last century, significant research has been focused on mechanisms and risk factors relevant to the multifaceted etiopathogenesis of neurodegenerative diseases. Currently, neurodegenerative diseases are incurable, and the treatments available only control the symptoms or delay the progression of the disease. This review is aimed at characterizing the complex network of molecular mechanisms underpinning acute and chronic neurodegeneration, focusing on the disturbance in redox homeostasis, as a common mechanism behind five pivotal risk factors: aging, oxidative stress, inflammation, glycation, and vascular injury. Considering the complex multifactorial nature of neurodegenerative diseases, a preventive strategy able to simultaneously target multiple risk factors and disease mechanisms at an early stage is most likely to be effective to slow/halt the progression of neurodegenerative diseases., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Patrizia Hrelia et al.)
- Published
- 2020
- Full Text
- View/download PDF
47. Oxidation-reduction mechanisms in psychiatric disorders: A novel target for pharmacological intervention.
- Author
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Rossetti AC, Paladini MS, Riva MA, and Molteni R
- Subjects
- Animals, Central Nervous System metabolism, Central Nervous System physiopathology, Humans, Mental Disorders metabolism, Mental Disorders physiopathology, Mental Disorders psychology, Oxidation-Reduction, Antioxidants therapeutic use, Central Nervous System drug effects, Central Nervous System Agents therapeutic use, Mental Disorders drug therapy, Oxidative Stress drug effects
- Abstract
While neurotransmitter dysfunction represents a key component in mental illnesses, there is now a wide agreement for a central pathophysiological hub that includes hormones, neuroinflammation, redox mechanisms as well as oxidative stress. With respect to oxidation-reduction (redox) mechanisms, preclinical and clinical evidence suggests that an imbalance in the pro/anti-oxidative homeostasis toward the increased production of substances with oxidizing potential may contribute to the etiology and manifestation of different psychiatric disorders. The substantial and continous demand for energy renders the brain highly susceptible to disturbances in its energy supply, especially following exposure to stressful events, which may lead to overproduction of reactive oxygen and nitrogen species under conditions of perturbed antioxidant defenses. This will eventually induce different molecular alterations, including extensive protein and lipid peroxidation, increased blood-brain barrier permeability and neuroinflammation, which may contribute to the changes in brain function and morphology observed in mental illnesses. This view may also reconcile different key concepts for psychiatric disorders, such as the neurodevelopmental origin of these diseases, as well as the vulnerability of selective cellular populations that are critical for specific functional abnormalities. The possibility to pharmacologically modulate the redox system is receiving increasing interest as a novel therapeutic strategy to counteract the detrimental effects of the unbalance in brain oxidative mechanisms. This review will describe the main mechanisms and mediators of the redox system and will examine the alterations of oxidative stress found in animal models of psychiatric disorders as well as in patients suffering from mental illnesses, such as schizophrenia and major depressive disorder. In addition, it will discuss studies that examined the effects of psychotropic drugs, including antipsychotics and antidepressants, on the oxidative balance as well as studies that investigated the effectiveness of a direct modulation of oxidative mechanisms in counteracting the behavioral and functional alterations associated with psychiatric disorders, which supports the promising role of the redox system as a novel therapeutic target for the improved treatment of brain disorders., Competing Interests: Declaration of Competing Interest M.A.R. has received compensation as speaker/consultant from Angelini, Lundbeck, Recordati, Sumitomo Dainippon Pharma and Sunovion, and he has received research grants from Sumitomo Dainippon Pharma and Sunovion. The other authors declare no financial interest or potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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48. Prokineticin 2 promotes and sustains neuroinflammation in vincristine treated mice: Focus on pain and emotional like behavior.
- Author
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Moschetti G, Amodeo G, Paladini MS, Molteni R, Balboni G, Panerai A, Sacerdote P, and Franchi S
- Subjects
- Animals, Anxiety chemically induced, Anxiety metabolism, Behavior, Animal drug effects, Cytokines metabolism, Depression chemically induced, Depression metabolism, Disease Models, Animal, Hyperalgesia chemically induced, Hyperalgesia metabolism, Male, Mice, Mice, Inbred C57BL, Neuroimmunomodulation drug effects, Random Allocation, Sciatic Nerve drug effects, Sciatic Nerve metabolism, Spinal Cord drug effects, Spinal Cord metabolism, Gastrointestinal Hormones metabolism, Neuralgia chemically induced, Neuralgia metabolism, Neuropeptides metabolism, Vincristine toxicity
- Abstract
Vincristine (VCR) treatment is often associated to painful neuropathy. Its development is independent from antitumoral mechanism and involves neuroinflammation. We investigated the role of the chemokine prokineticin (PK)2 in a mouse model of VCR induced neuropathy using a PK-receptors (PK-R) antagonist to counteract its development. We also evaluated emotional like deficits in VCR mice. VCR (0,1 mg/kg) was i.p. injected in C57BL/6J male mice once a day for 14 consecutive days. Pain, anxiety and depressive like behaviors were assessed in animals. PK2, PK-Rs, cytokines, neuroinflammatory markers (CD68, CD11b, GFAP, TLR4) and ATF3 were evaluated in DRG, spinal cord, prefrontal cortex and hippocampus. The PK-Rs antagonist PC1, was s.c. injected (150 μg/kg) twice a day from day 7 (hypersensitivity state) until day 14. Its effect on pain and neuroinflammation was evaluated. VCR mice developed neuropathic pain but not mood alterations. After 7 days of VCR treatment we observed a neuroinflammatory condition in DRG with high levels of PK-Rs, TLR4, CD68, ATF3 and IL-1β without relevant alterations in spinal cord. At day 14, an upregulation of PK system and a marked neuroinflammation was evident also in spinal cord. Moreover, at the same time, we observed initial alterations in supraspinal brain areas. PC1 treatment significantly counteracted neuropathic pain and blunted neuroinflammation., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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49. VEGF, IGF-1 and FGF-2 Serum Levels in Children and Adolescents with Autism Spectrum Disorder with and without Bipolar Disorder.
- Author
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Guldiken G, Karayagmurlu A, Kucukgergin C, and Coskun M
- Subjects
- Humans, Child, Male, Adolescent, Female, Severity of Illness Index, Biomarkers blood, Autism Spectrum Disorder blood, Bipolar Disorder blood, Fibroblast Growth Factor 2 blood, Insulin-Like Growth Factor I analysis, Insulin-Like Growth Factor I metabolism, Vascular Endothelial Growth Factor A blood
- Abstract
Purpose: To investigate serum levels of VEGF, IGF-1 and FGF-2, and relationships with several clinical characteristics in children and adolescents with autism spectrum disorder (ASD) with and without bipolar disorder (BD)., Method: 40 subjects with ASD + BD as study group, and 40 subjects with ASD as control group were included. Serum levels of VEGF, IGF-1, and FGF-2 were measured using commercial enzyme-linked immunosorbent assay kits., Results: The study group was significantly higher than the control group in terms of ASD severity, self-harming behavior and sleep disturbance. Serum VEGF and FGF-2 levels were significantly higher in the ASD + BD group than in the control group. There was no significant difference in serum IGF-1 levels between the two groups. There was no correlation between VEGF, IGF-1 and FGF-2 serum levels and ASD severity in the study group. However there was a negative correlation between VEGF levels and age at first diagnosis of BD, and a positive correlation between IGF-1 levels and the number of bipolar episodes in the study group., Conclusion: Growth factors like VEGF and FGF-2 may be potential biomarkers of bipolar disorder in young subjects with ASD. Given the difficulty of clinical management of BD in young subjects with ASD, potential biomarkers would help clinicians in the diagnosis and follow up of BD in this special population. Further research is needed whether VEGF and FGF-2 can be potential biomarkers in the clinical management of young subjects with ASD and BD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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50. Pathophysiology of leukocyte-tissue interactions
- Author
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MOLTENI R, FABBRI M, BENDER JR, PARDI , RUGGERO, Molteni, R, Fabbri, M, Bender, Jr, and Pardi, Ruggero
- Abstract
Unlike most somatic cells, leukocytes are constitutively non-adherent. However, adhesive interactions are not only a required step in essentially all effector functions performed by leukocytes, but they also relay increasingly well-defined intracellular signals that affect the leukocyte as well as the surrounding tissues. Dissecting such signals in leukocytes has provided a wealth of information that contributes to our understanding of how adhesion controls higher-order biological responses, ranging from cell migration to proliferation, differentiation and survival.
- Published
- 2006
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