- Neonatal and fetal brain pathology
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Cell death mechanisms and regulation
- Neonatal Respiratory Health Research
- Anesthesia and Neurotoxicity Research
- Chemical Synthesis and Reactions
- Cancer, Lipids, and Metabolism
- Mesoporous Materials and Catalysis
- Circadian rhythm and melatonin
- Neuroscience of respiration and sleep
- Prostate Cancer Treatment and Research
- Birth, Development, and Health
- Multicomponent Synthesis of Heterocycles
- MicroRNA in disease regulation
- DNA Repair Mechanisms
- Radiopharmaceutical Chemistry and Applications
- Synthesis and biological activity
- Sirtuins and Resveratrol in Medicine
- Inorganic and Organometallic Chemistry
- Cannabis and Cannabinoid Research
- Extracellular vesicles in disease
- Endoplasmic Reticulum Stress and Disease
- Circular RNAs in diseases
- Cancer Cells and Metastasis
University of Urbino
2016-2025
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
2013-2022
Istituti di Ricovero e Cura a Carattere Scientifico
2013-2022
Institute of Pharmacology
2009
Ospedale G.B. Morgagni - L.Pierantoni
2006
Mario Negri Institute for Pharmacological Research
2003
University of Milan
2003
University of Parma
1997-2002
Università di Camerino
1998
We have previously shown that in neonatal rats subjected to hypoxia-ischemia (HI) rapamycin administration increases autophagy, decreases apoptosis and significantly reduces brain damage. After HI, when autophagy is blocked neuronal cells rapidly progress toward necrotic cell death. The present study was undertaken assess the potential role of activation autophagic phosphatidylinositol 3-kinase (PI3K)/Akt kinase pathways neuroprotective effect rapamycin. Rapamycin caused a significant...
Abstract: Among the main factors responsible for perinatal brain injury, inflammation, hypoxia‐ischemia and formation of free radicals (FR) appear to play key roles. Melatonin, an endogenously produced indoleamine formed in higher amounts adults than neonates, is a potent FR scavenger as well indirect antioxidant. Herein, we examined whether melatonin provides significant protection against damage its long‐term consequences neonatal model (HI). Seven day‐old rats were subjected permanent...
Maternal infection/inflammation represents one of the most important factors involved in etiology brain injury newborns. We investigated modulating effect prenatal melatonin on neonatal inflammation process resulting from maternal intraperitoneal (i.p.) lipopolysaccharide (LPS) injections. LPS (300 μg/kg) was administered to pregnant rats at gestational days 19 and 20. Melatonin (5 mg/kg) i.p. same time as LPS. counteracted sensitization a second ibotenate-induced excitotoxic insult...
Conditions that interfere with the endoplasmic reticulum (ER) functions cause accumulation of unfolded proteins in ER lumen, referred to as stress, and activate a homeostatic signaling network known protein response (UPR). We have previously shown neonatal rats subjected hypoxia-ischemia (HI), melatonin administration significantly reduces brain damage. This study assessed whether attenuation stress is involved neuroprotective effect after HI. found UPR was strongly activated Melatonin...
Abstract Mitochondrial dysfunction is considered one of the hallmarks ischemia/reperfusion injury. Mitochondria are plastic organelles that undergo continuous biogenesis, fusion, and fission. They can be transferred between cells through tunneling nanotubes (TNTs), dynamic structures allow exchange proteins, soluble molecules, organelles. Maintaining mitochondrial dynamics crucial to cell function survival. The present study aimed assess effects melatonin on dynamics, TNT formation,...
Objective: Oxidative stress (OS) plays a key role in perinatal brain damage. The aim of this study is to evaluate the effectiveness melatonin as neuroprotective drug by investigating influence on OS and inflammation biomarkers an animal model cerebral hypoxia-ischemia. Methods: Five minutes after hypoxic-ischemic (HI) injury was administered 28 rats (HI-Mel group). At same time, were vehicle-treated (V-HI used sham operated controls (CTL). biomarkers: isoprostanes (IsoPs), neuroprostanes...
Abstract Introduction Neonates with hypoxic‐ischemic encephalopathy (HIE) undergoing hypothermia may benefit from adjunctive therapy melatonin. However, melatonin safety, pharmacokinetics (PK), and dosage in this sensitive population are still unknown. Methods results This study assessed the PK safety of enteral administration to neonates HIE hypothermia. Melatonin was infused at 0.5 mg/kg five Infusion started 1 hour after reached target temperature 33.5°C. Blood samples were collected...
The interaction among autophagy, apoptosis and necrosis is complex still a matter of debate. We have recently studied this after neonatal hypoxia-ischemia (HI) in rats. found that autophagic apoptotic pathways were significantly increased at short times HI neuronal cells. 3-Methyladenine (3-MA) wortmannin (WM), which inhibit reduced pathway activation switched the mechanism cell death from to necrotic. Rapamycin, conversely, increases necrotic death, decreased brain injury. A prophylactic...
Abstract Sorafenib is a multikinase inhibitor that has shown promising therapeutic results in different tumor histotypes, both as single agent or combination with other treatments. We analyzed the vitro activity of sorafenib pancreatic cancer, one most lethal and chemo‐radio‐resistant tumors, using four human cancer cell lines (t3m4, Capan 1, 2, MiaPaca 2), characterized by K‐ras gene status RAF/MEK/ERK profile. exerted strong anti‐proliferative effect independently RAS/RAF/MEK/ERK induced...
Abstract: Oxidative stress due to free radical formation and initiation of abnormal oxidative reactions is involved in several diseases newborns, such as hypoxic–ischemic encephalopathy. Melatonin, an endogenously produced indoleamine primarily formed the pineal gland, a potent scavenger well indirect antioxidant. The present study was conducted evaluate damage mediators possible effect melatonin treatment model encephalopathy 7‐day‐old rats. Pups were subjected permanent ligation right...
The androgen receptor (AR) represents the primary target for prostate cancer (PC) treatment even when disease progresses toward androgen-independent (AIPC) or castration-resistant (CRPC) forms. Because small chemical changes in structure of nonsteroidal AR ligands determine pharmacological responses AR, we developed a novel stereoselective synthetic strategy that allows sterically hindered C2-substituted bicalutamide analogues to be obtained. Biological and theoretical evaluations...
Melatonin possesses potential efficacy in perinatal brain injuries, and has been proposed as adjunctive pharmacological therapy combination with hypothermia the clinical setting. However, pharmacokinetics of melatonin preterm term newborns is still unknown. The aim this study was to analyze after intragastric administration infants. Preterm were enrolled 24-72 h birth, randomly assigned three groups receiving a single bolus 0.5 mg·kg-1 melatonin, or 3 boluses 1 5 at 24-h intervals. Blood...
Increasing evidence indicates that melatonin possesses protective effects toward different kinds of damage in various organs, including the brain. In a neonatal model hypoxia-ischemia (HI), was neuroprotective and preserved expression silent information regulator 1 (SIRT1) 24 hours after insult. This study aimed to gain more insight into role SIRT1 effect HI by studying early (1 hour) modulation its downstream targets, consequences on necrosis, apoptosis, autophagy, glial cell activation. We...
Prophylactic administration of simvastatin has been shown to protect against brain damage and its long-lasting behavioral consequences in neonatal rats. To establish the drug treatment window, we evaluated effectiveness administered at different intervals before after stroke. Furthermore, determined whether affected endothelial nitric oxide synthase (eNOS) or inflammatory cytokines tissue cholesterol levels serum.On postnatal day 7, male rats were subjected hypoxia-ischemia (HI). The...
Abstract Background Despite the great advances in understanding of programmed cell death, little attention has been paid to sequence events that characterise it. In particular, course apoptotic induced by microtubule-interfering agents such as taxanes is poorly understood. order increase knowledge, we studied a number independent biochemical and cytological modifications using cytometric methods bladder cancer line treated with second generation taxane, docetaxel. Results Within few hours,...