- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Autophagy in Disease and Therapy
- Sphingolipid Metabolism and Signaling
- Adipose Tissue and Metabolism
- Nitric Oxide and Endothelin Effects
- Immune cells in cancer
- Nanoparticle-Based Drug Delivery
- Genetics and Neurodevelopmental Disorders
- Endoplasmic Reticulum Stress and Disease
- Lipid Membrane Structure and Behavior
- ATP Synthase and ATPases Research
- Exercise and Physiological Responses
- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
- Mesenchymal stem cell research
- Birth, Development, and Health
- Histone Deacetylase Inhibitors Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Biosensing Techniques and Applications
- Adenosine and Purinergic Signaling
- Bioactive Compounds and Antitumor Agents
- Neurogenetic and Muscular Disorders Research
- Sirtuins and Resveratrol in Medicine
University of Milan
2015-2025
Luigi Sacco Hospital
2010-2023
ASST Fatebenefratelli Sacco
2016-2020
National Research Council
2012-2016
Institute of Molecular Science and Technologies
2010
University of Milano-Bicocca
2010
IRCCS Eugenio Medea
2005-2009
University of Calabria
2004-2006
University of Florence
2005
San Raffaele University of Rome
2005
Intrauterine growth restriction (IUGR) and pregnancy hypertensive disorders such as preeclampsia (PE) associated with IUGR share a common placental phenotype called “placental insufficiency”, originating in early gestation when high availability of energy is required. Here, we assess mitochondrial content the expression activity respiratory chain complexes (RCC) cells these pathologies. We measured (mt)DNA nuclear factor 1 ( NRF1) tissue cytotrophoblast cells, gene protein expressions RCC...
Abstract Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active the HER2 receptor is demonstrated in vitro and vivo a subcutaneous MCF-7 breast cancer mouse model trastuzumab-functionalized gold nanoparticles. The number attached antibodies per nanoparticle was precisely controlled way that each conjugated either exactly one or two As expected, we found moderate increase efficiency instead just antibody nanoparticle. However,...
Abstract Mitochondrial fission and fusion are essential processes in the maintenance of skeletal muscle function. The contribution these to development has not been properly investigated vivo because early lethality models generated so far. To define role mitochondrial repair, we have a transgenic mouse line that overexpresses fission-inducing protein Drp1 specifically muscle. These mice displayed drastic impairment postnatal growth, with reorganisation network reduction mtDNA quantity,...
The endocrine system participates in regulating macrophage maturation, although little is known about the modulating role of thyroid hormones. In vitro results demonstrate a negative one such hormone, triiodothyronine (T3), triggering differentiation bone marrow–derived monocytes into unpolarized macrophages. T3-induced macrophages displayed classically activated (M1) signature. A M1-priming effect was also observed on polarized because T3 reverses alternatively (M2) activation, whereas it...
Tumor microenvironment is fundamental for cancer progression and chemoresistance. Among stromal cells tumor-associated macrophages (TAMs) represent the largest population of infiltrating inflammatory in malignant tumors, promoting their growth, invasion immune evasion. M2-polarized TAMs are endowed with NO generating enzyme iNOS. has divergent effects on since it can either stimulate tumor growth or promote death depending source it; likewise role iNOS differs cell type. The generated by TAM...
Objective— Tumor necrosis factor α (TNF-α), a key proinflammatory cytokine acting on the endothelium, activates endothelial nitric oxide synthase (eNOS). We have examined signaling pathway leading to this activation and its biological role in which are still unknown. Methods Results— In human cells, we found that eNOS by TNF-α is time dependent requires of Akt, known activator. was preceded sequential neutral-sphingomyelinase-2 (N-SMase2) sphingosine-kinase-1 (SK1) generation...
During myogenic differentiation the short mitochondria of myoblasts change into extensively elongated network observed in myotubes. The functional relevance and molecular mechanisms driving formation this mitochondrial are unknown. We now show that elongation is required for myogenesis to occur event depends on cellular generation nitric oxide (NO). Inhibition NO synthesis precursor cells leads inhibition differentiation. This due enhanced activity, translocation docking pro-fission GTPase...
A great challenge in nanodiagnostics is the identification of new strategies aimed to optimize detection primary breast cancer and metastases by employment target-specific nanodevices. At present, controversial proof has been provided on actual importance surface functionalization nanoparticles improve their vivo localization at tumor. In present paper, we have designed developed a set multifunctional nanoprobes, modified with three different variants model antibody, that is, humanized...
Autophagy occurs at a basal level in all eukaryotic cells and may support cell survival or activate death pathways. Due to its pathophysiologic significance, the autophagic machinery is promising target for development of multiple approaches anti-neoplastic agents. We have recently described cytotoxic pro-apoptotic mechanisms, targeting tumour suppressor p53, climacostol, natural product ciliated protozoan Climacostomum virens. report here on how climacostol regulates autophagy involvement...
Nitric oxide (NO), generated in skeletal muscle mostly by the neuronal NO synthases (nNOSμ), has profound effects on both mitochondrial bioenergetics and development function. The importance of for repair emerges from observation that nNOS signalling is defective many genetically diverse diseases which dysregulated. How NO/nNOSμ mitochondria impact function, however, not been investigated yet.In this study we have examined relationship between system, structure/activity...
The mechanism of skeletal myoblast fusion is not well understood. We show that endogenous nitric oxide (NO) generation required for both in embryonic myoblasts and satellite cells. effect NO concentration time dependent, being evident only at the onset differentiation, direct on process itself. action mediated through a tightly regulated activation guanylate cyclase cyclic guanosine monophosphate (cGMP), so much deregulation cGMP signaling leads to fusion-induced hypertrophy...
Primary lateral sclerosis (PLS) is a rare progressive paralytic disorder that results from dysfunction of the upper motoneurons. Although PLS sporadic adult middle age, it has also been described in children as juvenile or JPLS. The causative gene for JPLS was found to be ALS2, which responsible recessive form amyotrophic sclerosis, infantile onset ascending hereditary spastic paralysis (IAHSP) and complicated paraplegia (cHSP). ALS2 encodes protein termed alsin, containing multiple guanine...
Highly monodisperse magnetite nanocrystals (MNC) were synthesized in organic media and transferred to the water phase by ultrasound-assisted ligand exchange with an iminodiacetic phosphonate. The resulting biocompatible magnetic nanoparticles characterized transmission electron microscopy, dynamic light scattering, magnetorelaxometry, indicating that this method allowed us obtain stable particle dispersions narrow size distribution unusually high resonance T2 contrast power. These conjugated...
Subcellular destiny of targeted nanoparticles in cancer cells within living organisms is still an open matter debate. By vivo and ex experiments on tumor-bearing mice treated with antibody-engineered magnetofluorescent nanocrystals, which we combined fluorescence imaging, magnetic relaxation, trasmission electron microscopy approaches, provide evidence that are effectively delivered to the tumor by active targeting. These nanocrystals were demonstrated enable contrast enhancement resonance...
Mitochondria play a critical role in neuronal function and neurodegenerative disorders, including Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis Huntington, that show mitochondrial dysfunctions associated with excessive fission increased levels of the protein Drp1. Our data demonstrate Drp1 regulates transcriptional program induced by retinoic acid, leading to differentiation. When was overexpressed, mitochondria underwent remodeling, but failed elongate this enhanced...
Abstract SEPN1-related myopathy (SEPN1-RM) is a muscle disorder due to mutations of the SEPN1 gene, which characterized by weakness and fatigue leading scoliosis life-threatening respiratory failure. Core lesions, focal areas mitochondria depletion in skeletal fibers, are most common histopathological lesion. SEPN1-RM underlying mechanisms precise role remained incompletely understood, hindering development biomarkers therapies for this untreatable disease. To investigate pathophysiological...
Synaptic abnormalities are a hallmark of several neurological diseases, and clarification the underlying mechanisms represents crucial step toward development therapeutic strategies. Rett syndrome (RTT) is rare neurodevelopmental disorder, mainly affecting females, caused by mutations in X-linked methyl-CpG-binding protein 2 (
Abstract Depletion of dendritic cells (DCs) via apoptosis contributes to sepsis-induced immune suppression. The mechanisms leading DC during sepsis are not known. In this study we report that immature DCs undergo when treated with high numbers Escherichia coli. This effect was mimicked by concentrations LPS. Apoptosis accompanied generation ceramide through activation acid sphingomyelinase (A-SMase), prevented inhibitors enzyme, and restored exogenous ceramide. Compared DCs, mature expressed...
Regeneration of muscle fibers, lost during pathological degeneration or after injuries, is mediated by the production new myofibres. This process, sustained resident stem cells muscle, satellite cells, finely regulated local cues, in particular cytokines and growth factors. Evidence literature suggests that nerve factor (NGF) involved fiber regeneration; however, its role mechanism action were unclear. We have investigated this issue vivo mouse models regeneration primary myogenic cells. Our...