Martina Bartolucci
@gaslini.org
Istituto Giannina Gaslini
Scopus Publications
Scopus Publications
Chiara Panicucci, Eray Sahin, Martina Bartolucci, Sara Casalini, Noemi Brolatti, Marina Pedemonte, Serena Baratto, Sara Pintus, Elisa Principi, Adele D’Amico,et al.
Springer Science and Business Media LLC
Abstract Aim The availability of disease-modifying therapies and newborn screening programs for spinal muscular atrophy (SMA) has generated an urgent need for reliable prognostic biomarkers to classify patients according to disease severity. We aim to identify cerebrospinal fluid (CSF) prognostic protein biomarkers in CSF samples of SMA patients collected at baseline (T0), and to describe proteomic profile changes and biological pathways influenced by nusinersen before the sixth nusinersen infusion (T302). Methods In this multicenter retrospective longitudinal study, we employed an untargeted liquid chromatography mass spectrometry (LC-MS)-based proteomic approach on CSF samples collected from 61 SMA patients treated with nusinersen (SMA1 n=19, SMA2 n=19, SMA3 n=23) at T0 at T302. The Random Forest (RF) machine learning algorithm and pathway enrichment analysis were applied for analysis. Results The RF algorithm, applied to the protein expression profile of naïve patients, revealed several proteins that could classify the different types of SMA according to their differential abundance at T0. Analysis of changes in proteomic profiles identified a total of 147 differentially expressed proteins after nusinersen treatment in SMA1, 135 in SMA2, and 289 in SMA3. Overall, nusinersen-induced changes on proteomic profile were consistent with i) common effects observed in allSMA types (i.e. regulation of axonogenesis), and ii) disease severity-specific changes, namely regulation of glucose metabolism in SMA1, of coagulation processes in SMA2, and of complement cascade in SMA3. Conclusions This untargeted LC-MS proteomic profiling in the CSF of SMA patients revealed differences in protein expression in naïve patients and showed nusinersen-related modulation in several biological processes after 10 months of treatment. Further confirmatory studies are needed to validate these results in larger number of patients and over abroader timeframe.
Giorgia Senesi, Laura Guerricchio, Maddalena Ghelardoni, Nadia Bertola, Stefano Rebellato, Nicole Grinovero, Martina Bartolucci, Ambra Costa, Andrea Raimondi, Cristina Grange,et al.
Elsevier BV
Melis Emanet, Marie Celine Lefevre, Maria Cristina Ceccarelli, Matteo Battaglini, Alessio Carmignani, Francesco Schiavone, Attilio Marino, Daniele De Pasquale, Mirko Prato, Francesco De Boni,et al.
American Chemical Society (ACS)
Polydopamine nanoparticles (PDA NPs) are proposed as an anti-cancer tool against hepatocellular carcinoma through the combination of near-infrared (NIR)-mediated hyperthermia and loading with a chemotherapeutic drug, sorafenib (SRF). Cell membranes isolated from a liver cancer cell line (HepG2) have been exploited for the coating of the nanoparticles (thus obtaining CM–SRF–PDA NPs), to promote homotypic targeting toward cancer cells. The selective targeting ability and the combined photothermal and chemotherapeutic activity of the CM–SRF–PDA NPs following NIR irradiation have been evaluated on cell cultures in static and dynamic conditions, besides three-dimensional culture models. Eventually, the therapeutic effectiveness of the proposed approach has also been tested ex ovo on HepG2 spheroid-grafted quail embryos. This comprehensive investigation, supported by proteomic analysis, showed the effectiveness of the proposed nanoplatform and strongly suggests further pre-clinical testing in the treatment of liver cancer.
Mohit Rastogi, Martina Bartolucci, Marina Nanni, Michelangelo Aloisio, Diego Vozzi, Andrea Petretto, Andrea Contestabile, and Laura Cancedda
Elsevier BV
Margherita Montorsi, Carlotta Pucci, Daniele De Pasquale, Attilio Marino, Maria Cristina Ceccarelli, Martina Mazzuferi, Martina Bartolucci, Andrea Petretto, Mirko Prato, Doriana Debellis,et al.
Wiley
AbstractGlioblastoma multiforme (GBM) is the most aggressive brain cancer, characterized by a rapid and drug‐resistant progression. GBM “builds” around its primary core a genetically heterogeneous tumor‐microenvironment (TME), recruiting surrounding healthy brain cells by releasing various intercellular signals. Glioma‐associated microglia (GAM) represent the largest population of collaborating cells, which, in the TME, usually exhibit the anti‐inflammatory M2 phenotype, thus promoting an immunosuppressing environment that helps tumor growth. Conversely, “classically activated” M1 microglia could provide proinflammatory and antitumorigenic activity, expected to exert a beneficial effect in defeating glioblastoma. In this work, an immunotherapy approach based on proinflammatory modulation of the GAM phenotype is proposed, through a controlled and localized electrical stimulation. The developed strategy relies on the wireless ultrasonic excitation of polymeric piezoelectric nanoparticles coated with GBM cell membrane extracts, to exploit homotypic targeting in antiglioma applications. Such camouflaged nanotransducers locally generate electrical cues on GAM membranes, activating their M1 phenotype and ultimately triggering a promising anticancer activity. Collected findings open new perspectives in the modulation of immune cell activities through “smart” nanomaterials and, more specifically, provide an innovative auspicious tool in glioma immunotherapy.
Maurizio Bruschi, Simona Granata, Giovanni Candiano, Andrea Petretto, Martina Bartolucci, Xhuliana Kajana, Sonia Spinelli, Alberto Verlato, Michele Provenzano, and Gianluigi Zaza
MDPI AG
mTOR inhibitors (mTOR-Is) may induce proteinuria in kidney transplant recipients through podocyte damage. However, the mechanism has only been partially defined. Total cell lysates and supernatants of immortalized human podocytes treated with different doses of everolimus (EVE) (10, 100, 200, and 500 nM) for 24 h were subjected to mass spectrometry-based proteomics. Support vector machine and partial least squares discriminant analysis were used for data analysis. The results were validated in urine samples from 28 kidney transplant recipients receiving EVE as part of their immunosuppressive therapy. We identified more than 7000 differentially expressed proteins involved in several pathways, including kinases, cell cycle regulation, epithelial–mesenchymal transition, and protein synthesis, according to gene ontology. Among these, after statistical analysis, 65 showed an expression level significantly and directly correlated with EVE dosage. Polo-Like Kinase 1 (PLK1) content was increased, whereas osteopontin (SPP1) content was reduced in podocytes and supernatants in a dose-dependent manner and significantly correlated with EVE dose (p < 0.0001, FDR < 5%). Similar results were obtained in the urine of kidney transplant patients. This study analyzed the impact of different doses of mTOR-Is on podocytes, helping to understand not only the biological basis of their therapeutic effects but also the possible mechanisms underlying proteinuria.
Maria Giovanna Danieli, Marco Casciaro, Alberto Paladini, Martina Bartolucci, Martina Sordoni, Yehuda Shoenfeld, and Sebastiano Gangemi
Elsevier BV
Sonia Spinelli, Xhuliana Kajana, Andrea Garbarino, Martina Bartolucci, Andrea Petretto, Marco Pavanello, Enrico Verrina, Giovanni Candiano, Isabella Panfoli, and Maurizio Bruschi
MDPI AG
Pediatric pilocytic astrocytoma (PA) is the most common brain tumor in children. Complete resection provides a favorable prognosis, except for unresectable PA forms. There is an incomplete understanding of the molecular and cellular pathogenesis of PA. Potential biomarkers for PA patients, especially the non-BRAF-mutated ones are needed. Cerebrospinal fluid (CSF) is a valuable source of brain tumor biomarkers. Extracellular vesicles (EVs), circulating in CSF, express valuable disease targets. These can be isolated from CSF from waste extraventricular drainage (EVD). We analyzed the proteome of EVD CSF from PA, congenital hydrocephalus (CH, non-tumor control), or medulloblastoma (MB, unrelated tumoral control) patients. A total of 3072 proteins were identified, 47.1%, 65.6%, and 86.2% of which were expressed in the unprocessed total and in its large-EV (LEV), and small-EV (SEV) fractions. Bioinformatics identified 50 statistically significant proteins in the comparison between PA and HC, and PA and MB patients, in the same fractions. Kinase enrichment analysis predicted five enriched kinases involved in signaling. Among these, only Cyclin-dependent kinase 2 (CDK2) kinase was overexpressed in PA samples. PLS-DA highlighted the inactive carboxypeptidase-like protein X2 (CPXM2) and aquaporin-4 (AQP4) as statistically significant in all the comparisons, with CPXM2 being overexpressed (validated by ELISA and Western blot) and AQP4 downregulated in PA. These proteins were considered the most promising potential biomarkers for discriminating among pilocytic astrocytoma and unrelated tumoral (MB) or non-tumoral conditions in all the fractions examined, and are proposed to be prospectively validated in the plasma for translational medicine applications.
Alessio Carmignani, Matteo Battaglini, Martina Bartolucci, Andrea Petretto, Mirko Prato, and Gianni Ciofani
Elsevier BV
Alberto Potenzieri, Sara Uccella, Deborah Preiti, Matteo Pisoni, Silvia Rosati, Chiara Lavarello, Martina Bartolucci, Doriana Debellis, Federico Catalano, Andrea Petretto,et al.
American Association for the Advancement of Science (AAAS)
Besides recent advances in neonatal care, preterm newborns still develop sex-biased behavioral alterations. Preterms fail to receive placental insulin-like growth factor-1 (IGF-1), a major fetal growth hormone in utero, and low IGF-1 serum levels correlate with preterm poor neurodevelopmental outcomes. Here, we mimicked IGF-1 deficiency of preterm newborns in mice by perinatal administration of an IGF-1 receptor antagonist. This resulted in sex-biased brain microstructural, functional, and behavioral alterations, resembling those of ex-preterm children, which we characterized performing parallel mouse/human behavioral tests. Pharmacological enhancement of GABAergic tonic inhibition by the U.S. Food and Drug Administration–approved drug ganaxolone rescued functional/behavioral alterations in mice. Establishing an unprecedented mouse model of prematurity, our work dissects the mechanisms at the core of abnormal behaviors and identifies a readily translatable therapeutic strategy for preterm brain disorders.
Carlotta Pucci, Daniele De Pasquale, Andrea Degl'Innocenti, Margherita Montorsi, Andrea Desii, Marta Pero, Chiara Martinelli, Martina Bartolucci, Andrea Petretto, and Gianni Ciofani
Wiley
AbstractGlioblastoma (GBM) is a highly aggressive brain tumor known for its resistance to standard treatments. Despite surgery being a primary option, it often leads to incomplete removal and high recurrence rates. Photodynamic therapy (PDT) holds promise as an adjunctive treatment, but safety concerns and the need for high‐power lasers have limited its widespread use. This research addresses these challenges by introducing a novel PDT approach, using chlorin e6 (Ce6) enclosed in nanostructured lipid carriers (Ang‐Ce6‐NLCs) and targeted to GBM with the angiopep‐2 peptide. Remarkably, a single 5‐min irradiation session with LEDs at 660 nm and low power density (10 mW cm−2) proves effective against GBM, while reducing safety risks associated with high‐power lasers. Encapsulation improves Ce6 stability and performance in physiological environments, while angiopep‐2 targeting enhances delivery to GBM cells, maximizing treatment efficacy and minimizing off‐target effects. The findings demonstrate that Ang‐Ce6‐NLCs‐mediated PDT brings about a significant reduction in GBM cell viability, increases oxidative stress, reduces tumor migration, and enhances apoptosis. Overall, such treatment holds potential as a safe and efficient intraoperative removal of GBM infiltrating cells that cannot be reached by surgery, using low‐power LED light to minimize harm to surrounding healthy tissue while maximizing tumor treatment.
Özlem Şen, Melis Emanet, Martina Mazzuferi, Martina Bartolucci, Federico Catalano, Mirko Prato, Stefania Moscato, Attilio Marino, Daniele De Pasquale, Giammarino Pugliese,et al.
American Chemical Society (ACS)
Microglial cells play a critical role in glioblastoma multiforme (GBM) progression, which is considered a highly malignant brain cancer. The activation of microglia can either promote or inhibit GBM growth depending on the stage of the tumor development and on the microenvironment conditions. The current treatments for GBM have limited efficacy; therefore, there is an urgent need to develop novel and efficient strategies for drug delivery and targeting: in this context, a promising strategy consists of using nanoplatforms. This study investigates the microglial response and the therapeutic efficacy of dual-cell membrane-coated and doxorubicin-loaded hexagonal boron nitride nanoflakes tested on human microglia and GBM cells. Obtained results show promising therapeutic effects on glioma cells and an M2 microglia polarization, which refers to a specific phenotype or activation state that is associated with anti-inflammatory and tissue repair functions, highlighted through proteomic analysis.
Xhuliana Kajana, Sonia Spinelli, Andrea Garbarino, Ganna Balagura, Martina Bartolucci, Andrea Petretto, Marco Pavanello, Giovanni Candiano, Isabella Panfoli, and Maurizio Bruschi
MDPI AG
Cerebrospinal fluid (CSF) is a biochemical–clinical window into the brain. Unfortunately, its wide dynamic range, low protein concentration, and small sample quantity significantly limit the possibility of using it routinely. Extraventricular drainage (EVD) of CSF allows us to solve quantitative problems and to study the biological role of extracellular vesicles (EVs). In this study, we implemented bioinformatic analysis of our previous data of EVD of CSF and its EVs obtained from congenital hydrocephalus with the aim of identifying a comprehensive list of potential tumor and non-tumor biomarkers of central nervous system diseases. Among all proteins identified, those enriched in EVs are associated with synapses, synaptosomes, and nervous system diseases including gliomas, embryonal tumors, and epilepsy. Among these EV-enriched proteins, given the broad consensus present in the recent scientific literature, we validated syntaxin-binding protein 1 (STXBP1) as a marker of malignancy in EVD of CSF and its EVs from patients with pilocytic astrocytoma and medulloblastoma. Our results show that STXBP1 is negatively enriched in EVs compared to non-tumor diseases and its downregulation correlates with adverse outcomes. Further experiments are needed to validate this and other EV markers in the blood of pediatric patients for translational medicine applications.
Gianluigi Zaza, Flavia Neri, Maurizio Bruschi, Simona Granata, Andrea Petretto, Martina Bartolucci, Caterina di Bella, Giovanni Candiano, Giovanni Stallone, Loreto Gesualdo,et al.
Springer Science and Business Media LLC
AbstractRenal normothermic machine perfusion (NMP) is an organ preservation method based on the circulation of a warm (35–37 °C) perfusion solution through the renal vasculature to deliver oxygen and nutrients. However, its biological effects on marginal kidneys are unclear. We therefore used mass spectrometry to determine the proteomic profile of kidney tissue and urine from eight organs reconditioned for 120 min using a Kidney Assist device. Biopsies were taken during the pre-implantation histological evaluation (T-1), at the start of back table preparation (T0), and after 60 and 120 min of perfusion (T60, T120). Urine samples were collected at T0 (urine produced in the first 15 min after the beginning of normothermic reperfusion), T30, T60 and T120. Multiple algorithms, support vector machine learning and partial least squares discriminant analysis were used to select the most discriminative proteins during NMP. Statistical analysis revealed the upregulation of 169 proteins and the downregulation of 196 during NMP. Machine learning algorithms identified the top 50 most discriminative proteins, five of which were concomitantly upregulated (LXN, ETFB, NUDT3, CYCS and UQCRC1) and six downregulated (CFHR3, C1S, CFI, KNG1, SERPINC1 and F9) in the kidney and urine after NMP. Latexin (LXN), an endogenous carboxypeptidase inhibitor, resulted the most-upregulated protein at T120, and this result was confirmed by ELISA. In addition, functional analysis revealed that the most strongly upregulated proteins were involved in the oxidative phosphorylation system and ATP synthesis, whereas the downregulated proteins represented the complement system and coagulation cascade. Our proteomic analysis demonstrated that even brief periods of NMP induce remarkable metabolic and biochemical changes in marginal organs, which supports the use of this promising technique in the clinic.
Martina Morini, Federica Raggi, Martina Bartolucci, Andrea Petretto, Martina Ardito, Chiara Rossi, Daniela Segalerba, Alberto Garaventa, Alessandra Eva, Davide Cangelosi,et al.
MDPI AG
Neuroblastoma (NB) is the most common extracranial solid tumor during infancy, causing up to 10% of mortality in children; thus, identifying novel early and accurate diagnostic and prognostic biomarkers is mandatory. NB-derived exosomes carry proteins (Exo-prots) reflecting the status of the tumor cell of origin. The purpose of this study was to characterize, for the first time, the Exo-prots specifically expressed in NB patients associated with tumor phenotype and disease stage. We isolated exosomes from plasma specimens of 24 HR-NB patients and 24 low-risk (LR-NB) patients at diagnosis and of 24 age-matched healthy controls (CTRL). Exo-prot expression was measured by liquid chromatography–mass spectrometry. The data are available via ProteomeXchange (PXD042422). The NB patients had a different Exo-prot expression profile compared to the CTRL. The deregulated Exo-prots in the NB specimens acted mainly in the tumor-associated pathways. The HR-NB patients showed a different Exo-prot expression profile compared to the LR-NB patients, with the modulation of proteins involved in cell migration, proliferation and metastasis. NCAM, NCL, LUM and VASP demonstrated a diagnostic value in discriminating the NB patients from the CTRL; meanwhile, MYH9, FN1, CALR, AKAP12 and LTBP1 were able to differentiate between the HR-NB and LR-NB patients with high accuracy. Therefore, Exo-prots contribute to NB tumor development and to the aggressive metastatic NB phenotype.
Valentin Nica, Attilio Marino, Carlotta Pucci, Özlem Şen, Melis Emanet, Daniele De Pasquale, Alessio Carmignani, Andrea Petretto, Martina Bartolucci, Simone Lauciello,et al.
American Chemical Society (ACS)
Prostate malignancy represents the second leading cause of cancer-specific death among the male population worldwide. Herein, enhanced intracellular magnetic fluid hyperthermia is applied in vitro to treat prostate cancer (PCa) cells with minimum invasiveness and toxicity and highly specific targeting. We designed and optimized novel shape-anisotropic magnetic core–shell–shell nanoparticles (i.e., trimagnetic nanoparticles - TMNPs) with significant magnetothermal conversion following an exchange coupling effect to an external alternating magnetic field (AMF). The functional properties of the best candidate in terms of heating efficiency (i.e., Fe3O4@Mn0.5Zn0.5Fe2O4@CoFe2O4) were exploited following surface decoration with PCa cell membranes (CM) and/or LN1 cell-penetrating peptide (CPP). We demonstrated that the combination of biomimetic dual CM-CPP targeting and AMF responsiveness significantly induces caspase 9-mediated apoptosis of PCa cells. Furthermore, a downregulation of the cell cycle progression markers and a decrease of the migration rate in surviving cells were observed in response to the TMNP-assisted magnetic hyperthermia, suggesting a reduction in cancer cell aggressiveness.
Federica Raggi, Martina Bartolucci, Davide Cangelosi, Chiara Rossi, Simone Pelassa, Chiara Trincianti, Andrea Petretto, Giovanni Filocamo, Adele Civino, Alessandra Eva,et al.
Frontiers Media SA
IntroductionNew early low-invasive biomarkers are demanded for the management of Oligoarticular Juvenile Idiopathic Arthritis (OJIA), the most common chronic pediatric rheumatic disease in Western countries and a leading cause of disability. A deeper understanding of the molecular basis of OJIA pathophysiology is essential for identifying new biomarkers for earlier disease diagnosis and patient stratification and to guide targeted therapeutic intervention. Proteomic profiling of extracellular vesicles (EVs) released in biological fluids has recently emerged as a minimally invasive approach to elucidate adult arthritis pathogenic mechanisms and identify new biomarkers. However, EV-prot expression and potential as biomarkers in OJIA have not been explored. This study represents the first detailed longitudinal characterization of the EV-proteome in OJIA patients.MethodsFourty-five OJIA patients were recruited at disease onset and followed up for 24 months, and protein expression profiling was carried out by liquid chromatography-tandem mass spectrometry in EVs isolated from plasma (PL) and synovial fluid (SF) samples.ResultsWe first compared the EV-proteome of SF vs paired PL and identified a panel of EV-prots whose expression was significantly deregulated in SF. Interaction network and GO enrichment analyses performed on deregulated EV-prots through STRING database and ShinyGO webserver revealed enrichment in processes related to cartilage/bone metabolism and inflammation, suggesting their role in OJIA pathogenesis and potential value as early molecular indicators of OJIA development. Comparative analysis of the EV-proteome in PL and SF from OJIA patients vs PL from age/gender-matched control children was then carried out. We detected altered expression of a panel of EV-prots able to differentiate new-onset OJIA patients from control children, potentially representing a disease-associated signature measurable at both the systemic and local levels with diagnostic potential. Deregulated EV-prots were significantly associated with biological processes related to innate immunity, antigen processing and presentation, and cytoskeleton organization. Finally, we ran WGCNA on the SF- and PL-derived EV-prot datasets and identified a few EV-prot modules associated with different clinical parameters stratifying OJIA patients in distinct subgroups.DiscussionThese data provide novel mechanistic insights into OJIA pathophysiology and an important contribution in the search of new candidate molecular biomarkers for the disease.
Maurizio Bruschi, Simona Granata, Giovanni Candiano, Andrea Petretto, Martina Bartolucci, Gian Marco Ghiggeri, Giovanni Stallone, and Gianluigi Zaza
Frontiers Media SA
IntroductionTo better define the biological machinery associated with BK virus (BKV) infection, in kidney transplantation, we performed a proteomics analysis of urinary extracellular vesicles (EVs).MethodsTwenty-nine adult kidney transplant recipients (KTRs) with normal allograft function affected by BKV infection (15 with only viremia, 14 with viruria and viremia) and 15 controls (CTR, KTRs without BKV infection) were enrolled and randomly divided in a training cohort (12 BKV and 6 CTR) used for the mass spectrometry analysis of the EVs (microvesicles and exosomes) protein content and a testing cohort (17 BKV and 9 CTR) used for the biological validation of the proteomic results by ELISA. Bioinformatics and functional analysis revealed that several biological processes were enriched in BKV (including immunity, complement activation, renal fibrosis) and were able to discriminate BKV vs. CTR. Kinase was the only gene ontology annotation term including proteins less abundant in BKV (with SLK being the most significantly down-regulated protein). Non-linear support vector machine (SVM) learning and partial least squares discriminant analysis (PLS-DA) identified 36 proteins (including DNASE2, F12, AGT, CTSH, C4A, C7, FABP4, and BPNT1) able to discriminate the two study groups. The proteomic profile of KTRs with BKV viruria alone vs. viremia and viruria was quite similar. Enzyme-linked immunosorbent assay (ELISA) for SLK, BPNT1 and DNASE2, performed on testing cohort, validated proteomics results.DiscussionsOur pilot study demonstrated, for the first time, that BKV infection, also in the viruric state, can have a negative impact on the allograft and it suggested that, whether possible, an early preventive therapeutic strategy should be undertaken also in KTRs with viruria only. Our results, then, revealed new mechanistic insights into BKV infection and they selected potential biomarkers that should be tested in future studies with larger patients’ cohorts.
Matteo Battaglini, Natalia Feiner, Christos Tapeinos, Daniele De Pasquale, Carlotta Pucci, Attilio Marino, Martina Bartolucci, Andrea Petretto, Lorenzo Albertazzi, and Gianni Ciofani
Royal Society of Chemistry (RSC)
Lipid magnetic nanovectors in contact with biological fluids are immediately covered by proteins. During the passage across brain endothelial cells, these proteins are partially lost and a new protein corona is developed.
Maurizio Bruschi, Xhuliana Kajana, Andrea Petretto, Martina Bartolucci, Marco Pavanello, Gian Marco Ghiggeri, Isabella Panfoli, and Giovanni Candiano
MDPI AG
Medulloblastoma (MB) is the most common pediatric malignant central nervous system tumor. Overall survival in MB depends on treatment tuning. There is aneed for biomarkers of residual disease and recurrence. We analyzed the proteome of waste cerebrospinal fluid (CSF) from extraventricular drainage (EVD) from six children bearing various subtypes of MB and six controls needing EVD insertion for unrelated causes. Samples included total CSF, microvesicles, exosomes, and proteins captured by combinatorial peptide ligand library (CPLL). Liquid chromatography-coupled tandem mass spectrometry proteomics identified 3560 proteins in CSF from control and MB patients, 2412 (67.7%) of which were overlapping, and 346 (9.7%) and 805 (22.6%) were exclusive. Multidimensional scaling analysis discriminated samples. The weighted gene co-expression network analysis (WGCNA) identified those modules functionally associated with the samples. A ranked core of 192 proteins allowed distinguishing between control and MB samples. Machine learning highlighted long-chain fatty acid transport protein 4 (SLC27A4) and laminin B-type (LMNB1) as proteins that maximized the discrimination between control and MB samples. Machine learning WGCNA and support vector machine learning were able to distinguish between MB versus non-tumor/hemorrhagic controls. The two potential protein biomarkers for the discrimination between control and MB may guide therapy and predict recurrences, improving the MB patients’ quality of life.
Francesca Piaggio, Michela Croce, Francesco Reggiani, Paola Monti, Cinzia Bernardi, Marianna Ambrosio, Barbara Banelli, Mehmet Dogrusöz, Ralf Jockers, Domenico Bordo,et al.
Elsevier BV
Matteo Battaglini, Alessio Carmignani, Chiara Martinelli, Jamila Colica, Attilio Marino, Stefano Doccini, Valentina Mollo, Francesca Santoro, Martina Bartolucci, Andrea Petretto,et al.
Royal Society of Chemistry (RSC)
PDNPs elicit an antioxidant effect on healthy and ARSACS-derived fibroblasts, thus reducing ROS levels, ROS-induced apoptosis/necrosis, and ROS-induced mitochondrial impairments, and enhancing protein expression.
Carlotta Pucci, Attilio Marino, Özlem Şen, Daniele De Pasquale, Martina Bartolucci, Nerea Iturrioz-Rodríguez, Nicoletta di Leo, Giuseppe de Vito, Doriana Debellis, Andrea Petretto,et al.
Elsevier BV
Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, represents the most aggressive primary brain tumor. The complex genetic heterogeneity, the acquired drug resistance, and the presence of the blood-brain barrier (BBB) limit the efficacy of the current therapies, with effectiveness demonstrated only in a small subset of patients. To overcome these issues, here we propose an anticancer approach based on ultrasound-responsive drug-loaded organic piezoelectric nanoparticles. This anticancer nanoplatform consists of nutlin-3a-loaded ApoE-functionalized P(VDF-TrFE) nanoparticles, that can be remotely activated with ultrasound-based mechanical stimulations to induce drug release and to locally deliver anticancer electric cues. The combination of chemotherapy treatment with chronic piezoelectric stimulation resulted in activation of cell apoptosis and of anti-proliferation pathways, induction of cell necrosis, inhibition of cancer migration, and reduction of cell invasiveness in drug-resistant GBM cells. Obtained results pave the way for the use of innovative multifunctional nanomaterials in less invasive and more focused anticancer treatments, able to reduce drug resistance in GBM. STATEMENT OF SIGNIFICANCE: : Piezoelectric hybrid lipid-polymeric nanoparticles, efficiently encapsulating a non-genotoxic drug (nutlin-3a) and functionalized with a peptide (ApoE) that enhances their passage through the BBB, are proposed. Upon ultrasound stimulation, nanovectors resulted able to reduce cell migration, actin polymerization, and invasion ability of glioma cells, while fostering apoptotic and necrotic events. This wireless activation of anticancer action paves the way to a less invasive, more focused and efficient therapeutic strategy.
Maurizio Bruschi, Martina Bartolucci, Andrea Petretto, Francesca Buffelli, Xhuliana Kajana, Alessandro Parodi, Riccardo Carbone, Ezio Fulcheri, Luca Antonio Ramenghi, Isabella Panfoli,et al.
Springer Science and Business Media LLC
AbstractSpontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.
Maurizio Bruschi, Edoardo La Porta, Isabella Panfoli, Giovanni Candiano, Andrea Petretto, Enrico Vidal, Xhuliana Kajana, Martina Bartolucci, Simona Granata, Gian Marco Ghiggeri,et al.
Springer Science and Business Media LLC
AbstractPeritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by steroid resistant primary focal segmental glomerulosclerosis, a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed to identify a core list of 40 proteins, with ANXA13 as most promising potential biomarker, to distinguish, in our patient population, peritoneal dialysis effluent exosomes of FSGS from No FSGS patients (with 100% accuracy). Additionally, the Weight Gene Co-expression Network Analysis algorithm identified 17 proteins, with PTP4A1 as the most statistically significant biomarker associated to PD vintage and decreased PM function. Altogether, our data suggest that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery. The role of the proposed biomarkers in the PM pathology deserves further investigation. Our results need further investigations in a larger population to corroborate these findings and investigate a possible increased risk of PM loss of function or development of encapsulating peritoneal sclerosis in FSGS patients, thus to eventually carry out changes in PD treatment and management or implement new solutions.