172 results on '"Urbani, Andrea"'
Search Results
2. Cardiac electrical instability in Erdheim-Chester disease: a case report.
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Urbani, Andrea, Pensotti, Filippo, Castini, Diego, Magnani, Silvia, Simeoli, Pasquale Simone, Campochiaro, Corrado, Dagna, Lorenzo, Cappelletti, Alberto M, Sponzilli, Carlo, and Guazzi, Marco
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ERDHEIM-Chester disease , *CENTRAL nervous system , *PITUITARY gland , *LANDSCAPE changes , *PROTEIN kinases - Abstract
Erdheim-Chester disease (ECD) is a rare multisystemic disorder of non-Langerhans histiocytic cells with a pleomorphic clinical presentation. It affects bones, skin, central nervous system, pituitary gland, ocular tissue, kidneys and perirenal tissue and lungs. Cardiac involvement presents usually with pericardial effusion and right atrial masses, but rarely with conduction system infiltration and subsequent arrhythmic events. Following the discovery of mutations of activating signaling kinase proteins (BRAF, MEK, ALK), the therapeutic landscape has changed to a more precise targeted treatment. Currently vemurafenib is approved for patient with end-organ dysfunction and BRAF-V600E mutation and the prognosis has dramatically improved. Here we present a case of ECD with electrical instability as main clinically relevant manifestation of cardiac involvement. [ABSTRACT FROM AUTHOR]
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- 2022
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3. Pharmacological modulation of Kv1.3 potassium channel selectively triggers pathological B lymphocyte apoptosis in vivo in a genetic CLL model.
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Severin, Filippo, Urbani, Andrea, Varanita, Tatiana, Bachmann, Magdalena, Azzolini, Michele, Martini, Veronica, Pizzi, Marco, Tos, Angelo Paolo Dei, Frezzato, Federica, Mattarei, Andrea, Ghia, Paolo, Bertilaccio, Maria Teresa Sabrina, Gulbins, Erich, Paradisi, Cristina, Zoratti, Mario, Semenzato, Gianpietro Carlo, Leanza, Luigi, Trentin, Livio, and Szabò, Ildiko
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FLUDARABINE , *POTASSIUM channels , *B cells , *LYMPHOCYTOSIS , *GENETIC models , *TUMOR classification , *CHRONIC lymphocytic leukemia - Abstract
Background: Ion channels are emerging as promising oncological targets. The potassium channels Kv1.3 and IKCa are highly expressed in the plasma membrane and mitochondria of human chronic lymphocytic leukemia (CLL) cells, compared to healthy lymphocytes. In vitro, inhibition of mitoKv1.3 by PAPTP was shown to kill ex vivo primary human CLL cells, while targeting IKCa with TRAM-34 decreased CLL cell proliferation. Methods: Here we evaluated the effect of the above drugs in CLL cells from ibrutinib-resistant patients and in combination with Venetoclax, two drugs used in the clinical practice. The effects of the drugs were tested also in the Eμ-TCL1 genetic CLL murine model, characterized by a lympho-proliferative disease reminiscent of aggressive human CLL. Eμ-TCL1 mice showing overt disease state were treated with intraperitoneal injections of non-toxic 5 nmol/g PAPTP or 10 nmol/g TRAM-34 once a day and the number and percentage of pathological B cells (CD19+CD5+) in different, pathologically relevant body districts were determined. Results: We show that Kv1.3 expression correlates with sensitivity of the human and mouse neoplastic cells to PAPTP. Primary CLL cells from ibrutinib-resistant patients could be killed with PAPTP and this drug enhanced the effect of Venetoclax, by acting on mitoKv1.3 of the inner mitochondrial membrane and triggering rapid mitochondrial changes and cytochrome c release. In vivo, after 2 week- therapy of Eμ-TCL1 mice harboring distinct CLL clones, leukemia burden was reduced by more than 85%: the number and percentage of CLL B cells fall in the spleen and peritoneal cavity and in the peripheral blood, without signs of toxicity. Notably, CLL infiltration into liver and spleen and splenomegaly were also drastically reduced upon PAPTP treatment. In contrast, TRAM-34 did not exert any beneficial effect when administered in vivo to Eμ-TCL1 mice at non-toxic concentration. Conclusion: Altogether, by comparing vehicle versus compound effect in different Eμ-TCL1 animals bearing unique clones similarly to CLL patients, we conclude that PAPTP significantly reduced leukemia burden in CLL-relevant districts, even in animals with advanced stage of the disease. Our results thus identify PAPTP as a very promising drug for CLL treatment, even for the chemoresistant forms of the disease. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Emerging Direct Targeting β-Catenin Agents.
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Nalli, Marianna, Masci, Domiziana, Urbani, Andrea, La Regina, Giuseppe, and Silvestri, Romano
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SMALL molecules , *ANTINEOPLASTIC agents , *STRUCTURE-activity relationships , *CELL nuclei - Abstract
Aberrant accumulation of β-catenin in the cell nucleus as a result of deregulation of the Wnt/β-catenin pathway is found in various types of cancer. Direct β-catenin targeting agents are being researched despite obstacles; however, specific β-catenin drugs for clinical treatments have not been approved so far. We focused on direct β-catenin targeting of potential therapeutic value as anticancer agents. This review provides recent advances on small molecule β-catenin agents. Structure-activity relationships and biological activities of reported inhibitors are discussed. This work provides useful knowledge in the discovery of β-catenin agents. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Mapping of Urinary Volatile Organic Compounds by a Rapid Analytical Method Using Gas Chromatography Coupled to Ion Mobility Spectrometry (GC–IMS).
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Riccio, Giulia, Baroni, Silvia, Urbani, Andrea, and Greco, Viviana
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- 2022
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6. A quantitative method for the analysis of glycated and glutathionylated hemoglobin by matrix-assisted laser desorption ionization-time of flight mass spectrometry
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Biroccio, Antonino, Urbani, Andrea, Massoud, Renato, di Ilio, Carmine, Sacchetta, Paolo, Bernardini, Sergio, Cortese, Claudio, and Federici, Giorgio
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MASS (Physics) , *MASS spectrometry , *SPECTRUM analysis , *CHEMICAL ionization mass spectrometry - Abstract
Abstract: The quantization of glycated isoforms of hemoglobin has been increasingly used in clinical practice in recent years. Glycated hemoglobin is currently considered the most important measurement for long-term control of the glycemic state and it has become a reference tool for the management of diabetes. Glutathionylated hemoglobin is an increasingly clinically relevant covalent adduct of glutathione with β chain of the globin and its concentration has been correlated with oxidative stress. We have developed an innovative technique based on linear mode matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry for quantitative analysis of hemoglobin species. This method was applied to the quantification of glycated and glutathionylated hemoglobin. A rigorous comparison was pursued to evaluate the analytical performances in quantifying glycated hemoglobin in comparison to an established high-performance liquid chromatography method. Our results indicated a complete equivalence between the two methods. The same analysis enabled the quantitative determination of the glutathionylated hemoglobin fraction. This isoform was investigated in an adult Italian population (184 individuals, 101 males and 83 females), indicating a bimodal distribution of this species. In fact 65.22% of screened individuals had glutathionylated hemoglobin levels lower than 0.50% while 34.78% had glutathionylated hemoglobin levels higher than 0.50%. A semiautomatic robotic procedure was developed for fast analysis of a large number of samples. This is the first report of a quantitative application of linear MALDI-TOF mass spectrometry for the determination of glutathionylated hemoglobin in blood samples. This method allows fast screening of this hemoglobin isoform, therefore opening the route to explore its specificity and sensitivity as a molecular biomarker. [Copyright &y& Elsevier]
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- 2005
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7. A colorimetric determination for glycosidic and bile salt-based detergents: applications in membrane protein research
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Urbani, Andrea and Warne, Tony
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COLORIMETRIC analysis , *COLORIMETRY , *ANALYTICAL chemistry , *MEMBRANE proteins - Abstract
Abstract: Detergents are crucial to the isolation of integral membrane proteins. During membrane protein purification, it is useful to accurately quantify detergent, especially if concentration steps have been used. Previously, this has been difficult and time-consuming. We present a simple, rapid, and sensitive procedure for the quantification of glycosidic and bile salt-based detergents such as dodecylmaltoside, octylglucoside, and CHAPS. The method directly quantifies sugar or cholate moieties via colorimetric reactions with phenol and sulfuric acid. A number of detergents have been screened, and the assay has been validated in the presence of commonly used reagents. In addition to determining the overall detergent concentration in solution, the procedure allows accurate quantification of specific binding of glycosidic or bile salt-based detergents to purified membrane proteins. Both the colorimetric method and the radiometric 14C method were used to determine detergent binding to two integral membrane proteins: the cytochrome cbb3 oxidase from Pseudomonas stutzeri and the turkey β-adrenergic receptor. Both methods gave similar results. After separating monomeric glycosidic detergent from micellar solutions by ultrafiltration, we used the colorimetric method to determine the concentration of monomeric detergent present. We observed that values obtained are in close agreement with previously determined critical micelle concentrations. [Copyright &y& Elsevier]
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- 2005
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8. The cytochrome cbb3 from Pseudomonas stutzeri displays nitric oxide reductase activity.
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Forte, Elena, Urbani, Andrea, Saraste, Matti, Sarti, Paolo, Brunori, Maurizio, and Giuffrè, Alessandro
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CYTOCHROME oxidase , *PSEUDOMONAS , *NITRIC-oxide synthases - Abstract
Examines the structure of the cytochrome cbb&sub3; purified from Pseudomonas stutzeri. Presence of nitric oxide reductase (NOR) activity in the enzyme; Re-oxidation of cytochrome cbb&sub3; by NO; Similarities between NOR and cytochrome oxidase.
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- 2001
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9. Riluzole inhibits the persistent sodium current in mammalian CNS neurons.
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Urbani, Andrea and Belluzzi, Ottorino
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NEURONS , *CENTRAL nervous system - Abstract
The effects of 0.1-100 µM riluzole, a neuroprotective agent with anticonvulsant properties, were studied on neurons from rat brain cortex. Patch-clamp whole-cell recordings in voltage-clamp mode were performed on thin slices to examine the effects of the drug on a noninactivating (persistent) Na[sup +] current (/[sub Na,p]). /[sub Na,p] was selected because it enhances neuronal excitability near firing threshold, which makes it a potential target for anticonvulsant drugs. When added to the external solution, riluzole dose-dependently inhibited /[sub Na,p] up to a complete blocking of the current (EC[sub 50] 2 µM), showing a significant effect at therapeutic drug concentrations. A comparative dose-effect study was carried out in the same cells for the other main known action of riluzole, the inhibitory effect on the fast transient sodium current. This effect was confirmed in our experiments, but we found that it was achieved at levels much higher than putative therapeutic concentrations. Only the effect on/[sub Na,p], and not that on fast sodium current, can account for the reduction in neuronal excitability observed in cortical neurons following riluzole treatment at therapeutic concentrations, and this might represent a novel mechanism accounting for the anticonvulsant and neuroprotective properties of riluzole. [ABSTRACT FROM AUTHOR]
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- 2000
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10. Mitochondrial Biomarkers in the Omics Era: A Clinical-Pathophysiological Perspective.
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Gervasoni, Jacopo, Primiano, Aniello, Cicchinelli, Michela, Santucci, Lavinia, Servidei, Serenella, Urbani, Andrea, Primiano, Guido, and Iavarone, Federica
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BIOMARKERS , *MITOCHONDRIA , *METABOLOMICS , *ARCHAEOLOGICAL human remains , *PUBLISHED articles , *PROTEOMICS - Abstract
Mitochondrial diseases (MDs) affect 4300 individuals, with different ages of presentation and manifestation in any organ. How defects in mitochondria can cause such a diverse range of human diseases remains poorly understood. In recent years, several published research articles regarding the metabolic and protein profiles of these neurogenetic disorders have helped shed light on the pathogenetic mechanisms. By investigating different pathways in MDs, often with the aim of identifying disease biomarkers, it is possible to identify molecular processes underlying the disease. In this perspective, omics technologies such as proteomics and metabolomics considered in this review, can support unresolved mitochondrial questions, helping to improve outcomes for patients. [ABSTRACT FROM AUTHOR]
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- 2024
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11. A Novel ATM Pathogenic Variant in an Italian Woman with Gallbladder Cancer.
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De Paolis, Elisa, Urbani, Andrea, Salvatore, Lisa, Foca, Laura, Tortora, Giampaolo, Minucci, Angelo, and Concolino, Paola
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GALLBLADDER cancer , *TUMOR suppressor genes , *GENES , *ATAXIA telangiectasia , *AUTOMATED teller machines , *SOMATIC mutation - Abstract
Gallbladder carcinoma (GBC) is one of the most aggressive malignancies with poor prognosis and a high fatality rate. The disease presents in advanced stages where the treatment is ineffective. Regarding GBC pathogenesis, as with other neoplasia, this tumor is a multifactorial disorder involving different causative factors such as environmental, microbial, metabolic, and molecular. Genetic alterations can be germline or somatic that involving proto-oncogenes, tumor suppressor genes, cell cycle genes, and growth factors. The ataxia telangiectasia mutated (ATM) gene, coding a serine/threonine kinase involved in the early stages of the homologous recombination (HR) mechanism, is one of the most altered genes in GBC. Here, we present the molecular characterization of a novel germline ATM large genomic rearrangement (LGR) identified by next-generation sequencing (NGS) analysis in an Italian woman diagnosed with metastatic GBC at the age of 55. The results underline the importance of expanding the NGS approach in gallbladder cancer in order to propose new molecular markers of predisposition and prognosis exploitable by novel targeted therapies that may improve the response of patients with ATM-deficient cancers. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Multiple determinants influence complex formation of the hepatitis C virus NS3 protease domain...
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Urbani, Andrea and Biasiol, Gabriella
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HEPATITIS C virus , *PEPTIDES - Abstract
Describes the interaction of the hepatitis C virus (HCV) NS3 protease domain with its NS4A cofactor peptide at equilibrium and at pre-steady state under different physiochemical conditions. Extent of glycerol-induced stabilization varied in an HCV strain-dependent way with at least one determinant mapping to an NS3 interaction site.
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- 1999
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13. Complex formation between the hepatitis C virus serine protease and A synthetic NS4A cofactor...
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Bianchi, Elisabetta and Urbani, Andrea
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HEPATITIS C virus , *PROTEOLYTIC enzymes - Abstract
Examines the complex formation between the hepatitis C virus serine protease and A synthetic NS4A cofactor peptide. Maturation cleavages that occur in the nonstructural region of the viral protein; In vitro complex formation between the NS3 protease domain.
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- 1997
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14. A zinc binding site in viral serine proteinases.
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De Francesco, Raffaele and Urbani, Andrea
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SERINE proteinases , *HEPATITIS C virus , *ZINC - Abstract
Presents a homology model that predicts the components of the zinc binding site of the serine protease domain of NS3 protein of hepatitis C virus. Need of zinc for enzymatic activity; Properties of the metal-substituted NS3 proteinases.
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- 1996
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15. The Bee Gut Microbiota: Bridging Infective Agents Potential in the One Health Context.
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Tilocca, Bruno, Greco, Viviana, Piras, Cristian, Ceniti, Carlotta, Paonessa, Mariachiara, Musella, Vincenzo, Bava, Roberto, Palma, Ernesto, Morittu, Valeria Maria, Spina, Anna Antonella, Castagna, Fabio, Urbani, Andrea, Britti, Domenico, and Roncada, Paola
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GUT microbiome , *HONEYBEES , *BEES , *POLLUTION , *DRUG resistance in microorganisms , *ZOOLOGICAL specimens , *HEALTH promotion , *BEE colonies - Abstract
The bee gut microbiota plays an important role in the services the bees pay to the environment, humans and animals. Alongside, gut-associated microorganisms are vehiculated between apparently remote habitats, promoting microbial heterogeneity of the visited microcosms and the transfer of the microbial genetic elements. To date, no metaproteomics studies dealing with the functional bee microbiota are available. Here, we employ a metaproteomics approach to explore a fraction of the bacterial, fungal, and unicellular parasites inhabiting the bee gut. The bacterial community portrays a dynamic composition, accounting for specimens of human and animal concern. Their functional features highlight the vehiculation of virulence and antimicrobial resistance traits. The fungal and unicellular parasite fractions include environment- and animal-related specimens, whose metabolic activities support the spatial spreading of functional features. Host proteome depicts the major bee physiological activities, supporting the metaproteomics strategy for the simultaneous study of multiple microbial specimens and their host-crosstalks. Altogether, the present study provides a better definition of the structure and function of the bee gut microbiota, highlighting its impact in a variety of strategies aimed at improving/overcoming several current hot topic issues such as antimicrobial resistance, environmental pollution and the promotion of environmental health. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Essential oils from Anethum graveolens L. and their phytotoxic and antibiofilm potential.
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Polito, Flavio, Khammassi, Marwa, Kouki, Habiba, Amri, Ismail, Di Vito, Maura, Urbani, Andrea, Nazzaro, Filomena, Fratianni, Florinda, and De Feo, Vincenzo
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DILL , *ESSENTIAL oils , *GRAM-negative bacteria , *ESCHERICHIA coli , *ITALIAN ryegrass , *PATHOGENIC bacteria , *ACINETOBACTER baumannii , *WEEDS , *INFLORESCENCES - Abstract
Essential oils (EOs) from inflorescences (EO-i), stems (EO-s) and leaves (EO-l) of Anethum graveolens are analyzed by GC and GC-MS. The main components are α-phellandrene (51.44%) and p-cymene (22.65%) in the EO-i, p-cymene (50.75%) and α-phellandrene (35.73%) in EO-s and p-cymene (40.01%) and α-phellandrene (36.38%) in EO-l. The phytotoxic activity was tested against germination and growth of aerial parts and roots of dicotyledones (Sinapis arvensis and Trifolium campestre) and monocotyledone (Lolium multiflorum) weeds. The EOs proved to be particularly active against S. arvensis and T. campestre, causing total inhibition of germination and growth at the highest doses (2.0 and 1.5 μL/mL) with IC50 values included between 0.3 and 1.6 mg/mL. The antibacterial and antibiofilm activity was tested against Gram positive (Staphylococcus aureus subsp. aureus and Listeria monocytogenes) and Gram negative (Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli) pathogenic bacterial strains. EOs presented MICs lower than those of Tetracycline (20-24 mg/mL) against most bacterial strains (from 4 to 6 mg/mL). EOs were found to be active in inhibiting bacterial biofilm formation with IC50 values between 1.47 and 3.85 mg/mL. The activity against bacterial metabolism occurred for EO-i and EO-s against A. baumannii and E. coli with IC50 between 0.99 and 5.39 mg/mL. This investigation provides data about the chemical variation among different parts of A. graveolens and encourages the use of its EOs as natural phytotoxic and antibacterial agents in agriculture, food and pharmaceutical sectors. [ABSTRACT FROM AUTHOR]
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- 2024
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17. A novel risk score predicting 30‐day hospital re‐admission of patients with acute stroke by machine learning model.
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Mercurio, Giovanna, Gottardelli, Benedetta, Lenkowicz, Jacopo, Patarnello, Stefano, Bellavia, Simone, Scala, Irene, Rizzo, Pierandrea, de Belvis, Antonio Giulio, Del Signore, Anna Benedetta, Maviglia, Riccardo, Bocci, Maria Grazia, Olivi, Alessandro, Franceschi, Francesco, Urbani, Andrea, Calabresi, Paolo, Valentini, Vincenzo, Antonelli, Massimo, and Frisullo, Giovanni
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MACHINE learning , *DISEASE risk factors , *HOSPITAL care quality , *HOSPITAL patients , *RECEIVER operating characteristic curves - Abstract
Background: The 30‐day hospital re‐admission rate is a quality measure of hospital care to monitor the efficiency of the healthcare system. The hospital re‐admission of acute stroke (AS) patients is often associated with higher mortality rates, greater levels of disability and increased healthcare costs. The aim of our study was to identify predictors of unplanned 30‐day hospital re‐admissions after discharge of AS patients and define an early re‐admission risk score (RRS). Methods: This observational, retrospective study was performed on AS patients who were discharged between 2014 and 2019. Early re‐admission predictors were identified by machine learning models. The performances of these models were assessed by receiver operating characteristic curve analysis. Results: Of 7599 patients with AS, 3699 patients met the inclusion criteria, and 304 patients (8.22%) were re‐admitted within 30 days from discharge. After identifying the predictors of early re‐admission by logistic regression analysis, RRS was obtained and consisted of seven variables: hemoglobin level, atrial fibrillation, brain hemorrhage, discharge home, chronic obstructive pulmonary disease, one and more than one hospitalization in the previous year. The cohort of patients was then stratified into three risk categories: low (RRS = 0–1), medium (RRS = 2–3) and high (RRS >3) with re‐admission rates of 5%, 8% and 14%, respectively. Conclusions: The identification of risk factors for early re‐admission after AS and the elaboration of a score to stratify at discharge time the risk of re‐admission can provide a tool for clinicians to plan a personalized follow‐up and contain healthcare costs. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Focus on RAS Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis.
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Schietroma, Francesco, Anghelone, Annunziato, Valente, Giustina, Beccia, Viria, Caira, Giulia, Spring, Alexia, Trovato, Giovanni, Di Bello, Armando, Ceccarelli, Anna, Chiofalo, Laura, Perazzo, Serena, Bensi, Maria, Minucci, Angelo, Urbani, Andrea, Larocca, Luigi Maria, Basso, Michele, Pozzo, Carmelo, Salvatore, Lisa, Calegari, Maria Alessandra, and Tortora, Giampaolo
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RESEARCH funding , *SCIENTIFIC observation , *FISHER exact test , *COLORECTAL cancer , *RETROSPECTIVE studies , *CHI-squared test , *DESCRIPTIVE statistics , *CELLULAR signal transduction , *METASTASIS , *KAPLAN-Meier estimator , *LOG-rank test , *ONCOGENES , *MEDICAL records , *ACQUISITION of data , *GENETIC mutation , *DATA analysis software , *PHENOTYPES , *OVERALL survival , *SYMPTOMS - Abstract
Simple Summary: Codon 61 RAS mutations are rare in metastatic colorectal cancer. Despite being associated with primary and acquired resistance to anti-EGFR agents, little is known about their phenotype and prognostic impact. We retrospectively investigated the clinicopathological features and prognoses of 50 patients with tumors harboring codon 61 RAS mutations compared to 648 codon 61 RAS wild-type tumors. We identified a significant correlation between codon 61 RAS mutations and metastatic involvement of the peritoneum and ovary and a negative prognostic impact. This is the first evidence of an impact of RAS mutational status on the metastatization pattern. These results are of great interest given the high frequency of codon 61 RAS mutations as mechanisms of secondary resistance to anti-EGFRs and the advent of RAS inhibitors. This is the widest codon 61 RAS-mutated cohort reported so far; nevertheless, these findings must be validated in larger studies. RAS mutations involving codon 61 are rare in metastatic colorectal cancer (mCRC), accounting for only 1–4%, but they have recently been identified with high frequency in the circulating tumor DNA (ctDNA) of patients with secondary resistance to anti-EGFRs. This retrospective monocentric study aimed to investigate the clinical phenotype and prognostic performance of codon 61 RAS-mutated mCRC. Fifty patients with codon 61 RAS-mutated mCRC treated at our institution between January 2013 and December 2021 were enrolled. Additional datasets of codon 61 RAS wild-type mCRCs (648 patients) were used as comparators. The endpoint for prognostic assessment was overall survival (OS). Metastatic involvement of the peritoneum or ovary was significantly more frequent in codon 61 RAS-mutated mCRC compared to codon 61 RAS wild-type (54 vs. 28.5%), non-codon 61 RAS-mutated (35.6%), BRAF V600E-mutated (25%), and RAS/BRAF wild-type (20.5%) cohorts. At a median follow up of 96.2 months, the median OS for codon 61 RAS-mutated patients was significantly shorter compared to RAS/BRAF wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 RAS-mutated and BRAF V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 RAS mutations and metastatic involvement of the peritoneum and ovary. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Association between Plasma HLA-DR+ Placental Vesicles and Preeclampsia: A Pilot Longitudinal Cohort Study.
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Onori, Marianna, Franco, Rita, Lucchetti, Donatella, Tartaglia, Silvio, Buongiorno, Silvia, Beneduce, Giuliana, Sannino, Fabio, Baroni, Silvia, Urbani, Andrea, Lanzone, Antonio, Scambia, Giovanni, Di Simone, Nicoletta, and Tersigni, Chiara
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PREECLAMPSIA , *SECOND trimester of pregnancy , *HLA histocompatibility antigens , *THIRD trimester of pregnancy , *PREGNANT women , *PLACENTA - Abstract
(1) Background: Preeclampsia (PE) usually presents with hypertension and proteinuria, related to poor placentation. Reduced maternal–fetal immunological tolerance is a possible trigger of inadequate placentation. Aberrant antigen expression of HLA-DR has been observed in the syncytiotrophoblast of PE patients. In this study, we analyzed plasma levels of Human Leukocyte Antigen (HLA)-DR+ syncytiotrophoblast-derived extracellular vesicles (STEVs) during the three trimesters of pregnancy in relation to PE onset. (2) Methods: Pregnant women underwent venous blood sampling during the three trimesters. STEVs were collected from plasma via ultracentrifugation (120,000 g) and characterized by Western blot, nanotracking analysis and flow cytometry for the expression of Placental Alkaline Phosphatase (PLAP), a placental-derived marker, and HLA-DR. (3) Results: Out of 107 women recruited, 10 developed PE. STEVs were detected in all three trimesters of pregnancy with a zenith in the second trimester. A significant difference was found between the non-PE and PE groups in terms of plasma levels of HLA-DR+ STEVs during all three trimesters of pregnancy. (4) Conclusions: More research is needed to investigate HLA-DR+ as a potential early marker of PE. [ABSTRACT FROM AUTHOR]
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- 2024
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20. SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma.
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Teveroni, Emanuela, Di Nicuolo, Fiorella, Vergani, Edoardo, Oliva, Alessandro, Vodola, Emanuele Pierpaolo, Bianchetti, Giada, Maulucci, Giuseppe, De Spirito, Marco, Cenci, Tonia, Pierconti, Francesco, Gulino, Gaetano, Iavarone, Federica, Urbani, Andrea, Milardi, Domenico, Pontecorvi, Alfredo, and Mancini, Francesca
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SEMINOMA , *QUERYING (Computer science) , *TESTICULAR cancer , *MATRIX metalloproteinases , *CONFOCAL microscopy - Abstract
Seminoma is the most common testicular cancer. Pituitary tumor-transforming gene 1 (PTTG1) is a securin showing oncogenic activity in several tumors. We previously demonstrated that nuclear PTTG1 promotes seminoma tumor invasion through its transcriptional activity on matrix metalloproteinase 2 (MMP-2) and E-cadherin (CDH1). We wondered if specific interactors could affect its subcellular distribution. To this aim, we investigated the PTTG1 interactome in seminoma cell lines showing different PTTG1 nuclear levels correlated with invasive properties. A proteomic approach upon PTTG1 immunoprecipitation uncovered new specific securin interactors. Western blot, confocal microscopy, cytoplasmic/nuclear fractionation, sphere-forming assay, and Atlas database interrogation were performed to validate the proteomic results and to investigate the interplay between PTTG1 and newly uncovered partners. We observed that spectrin beta-chain (SPTBN1) and PTTG1 were cofactors, with SPTBN1 anchoring the securin in the cytoplasm. SPTBN1 downregulation determined PTTG1 nuclear translocation, promoting its invasive capability. Moreover, a PTTG1 deletion mutant lacking SPTBN1 binding was strongly localized in the nucleus. The Atlas database revealed that seminomas that contained higher nuclear PTTG1 levels showed significantly lower SPTBN1 levels in comparison to non-seminomas. In human seminoma specimens, we found a strong PTTG1/SPTBN1 colocalization that decreases in areas with nuclear PTTG1 distribution. Overall, these results suggest that SPTBN1, along with PTTG1, is a potential prognostic factor useful in the clinical management of seminoma. [ABSTRACT FROM AUTHOR]
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- 2023
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21. Microbial signature of plaque and gut in acute coronary syndrome.
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Pisano, Eugenia, Bugli, Francesca, Severino, Anna, Pedicino, Daniela, Paroni Sterbini, Francesco, Martini, Cecilia, De Maio, Flavio, Vinci, Ramona, Sacconi, Andrea, Canonico, Francesco, D'Aiello, Alessia, Bonanni, Alice, Proto, Luca, Ciampi, Pellegrino, Ponzo, Myriana, Grimaldi, Maria Chiara, Urbani, Andrea, Primiano, Aniello, Gervasoni, Jacopo, and Montone, Rocco
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ACUTE coronary syndrome , *FISHER discriminant analysis , *TRANSLUMINAL angioplasty , *CARDIOVASCULAR diseases risk factors , *PRINCIPAL components analysis - Abstract
Gut microbiota is an emerging editable cardiovascular risk factor. We aim to investigate gut and coronary plaque microbiota, using fecal samples and angioplasty balloons from patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and control subjects. We examined bacterial communities in gut and coronary plaques by 16S rRNA sequencing and we performed droplet digital PCR analysis to investigate the gut relative abundance of the bacterial genes CutC/CntA involved in trimethylamine N-oxide synthesis. Linear discriminant analysis effect size (LEfSe) at the genus and species levels displayed gut enrichment in Streptococcus, Granulicatella and P. distasonis in ACS compared with CCS and controls; Roseburia, C. aerofaciens and F. prausnitzii were more abundant in controls than in patients. Principal component analysis (PCA) of 41 differentially abundant gut taxa showed a clustering of the three groups. In coronary plaque, LEfSe at the genus level revealed an enrichment of Staphylococcus and Streptococcus in ACS, and Paracoccus in CCS, whereas PCA of 15 differentially abundant plaque taxa exhibited clustering of ACS and CCS patients. CutC and CntA genes were more abundant in ACS and CCS than in controls while no significant difference emerged between ACS and CCS. Our results indicate that ACS and CCS exhibit a different gut and plaque microbial signature, suggesting a possible role of these microbiotas in coronary plaque instability. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
22. Recent Advances in Drug Discovery for Triple-Negative Breast Cancer Treatment.
- Author
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Masci, Domiziana, Naro, Chiara, Puxeddu, Michela, Urbani, Andrea, Sette, Claudio, La Regina, Giuseppe, and Silvestri, Romano
- Subjects
- *
TRIPLE-negative breast cancer , *DRUG discovery , *CANCER treatment , *SMALL molecules , *BREAST cancer - Abstract
Triple-negative breast cancer (TNBC) is one of the most heterogeneous and aggressive breast cancer subtypes with a high risk of death on recurrence. To date, TNBC is very difficult to treat due to the lack of an effective targeted therapy. However, recent advances in the molecular characterization of TNBC are encouraging the development of novel drugs and therapeutic combinations for its therapeutic management. In the present review, we will provide an overview of the currently available standard therapies and new emerging therapeutic strategies against TNBC, highlighting the promises that newly developed small molecules, repositioned drugs, and combination therapies have of improving treatment efficacy against these tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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23. Ceramic-on-metal bearing in short stem total hip arthroplasty: ions, functional and radiographic evaluation at mid-term follow-up.
- Author
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Saracco, Michela, Maccauro, Giulio, Urbani, Andrea, Ciavardelli, Domenico, Persichilli, Silvia, Ancillai, Giulio, Pasqualetti, Patrizio, Calvisi, Vittorio, and Logroscino, Giandomenico
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PELVIC radiography , *ARTIFICIAL joints , *CHROMIUM , *COBALT , *HEAVY metals , *HIP joint diseases , *LEG length inequality , *LONGITUDINAL method , *META-analysis , *METAPLASTIC ossification , *OSTEOARTHRITIS , *PATIENTS , *SURGERY , *TOTAL hip replacement , *OSSEOINTEGRATION , *VISUAL analog scale , *TREATMENT effectiveness , *FUNCTIONAL assessment , *DESCRIPTIVE statistics , *EVALUATION - Abstract
Introduction: The aim of this study is to evaluate clinical, radiographic and laboratory results of ceramic-on-metal (CoM) (hybrid hard bearing) in total hip arthroplasty (THA), associated with a short stem implant. Methods: From a cohort of 37 patients suffering from primary or secondary hip osteoarthritis who underwent THA using CoM bearing, 19 were suitable for this study. All procedures were performed by the same surgeon using a posterior-lateral approach. All patients were compared clinically using the Harris Hip Score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS), 12-item Short Form Health Survey (SF12F/M), and radiographically (offset, CD angle, limb length discrepancy, cup inclination and anteversion, subsidence, osseointegration, heterotopic ossification). Blood samples were collected in order to evaluate chromium (Cr) and cobalt (Co) ions level. Radiographic evaluations were carried out by 3 different blinded surgeons. A statistical analysis was performed. Results: At a mean follow-up of 97 (73–125) months all implanted stems were well-positioned and osseointegrated. Clear improvements were observed for clinical scores comparing preoperative and postoperative values. Radiographic evaluation showed a good ability to restore proper articular geometry. Cr ion analysis revealed values below the safety threshold except for 1 case. Serum levels of Co were below the threshold in all patients. There was a statistically significant correlation only between Cr metal ions and length of follow-up. Conclusions: CoM bearing has proven to be reliable and safe at a mean 8-year follow-up for patients in whom the components were correctly implanted. The rise of blood metal ions was minimal and involved neither systemic or local toxicity nor influenced clinical results. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
24. Molecular nature and regulation of the mitochondrial permeability transition pore(s), drug target(s) in cardioprotection.
- Author
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Carraro, Michela, Carrer, Andrea, Urbani, Andrea, and Bernardi, Paolo
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PERMEABILITY , *DRUG target , *EXTRACELLULAR matrix proteins , *ADENINE , *SITE-specific mutagenesis , *SMALL molecules - Abstract
The mitochondrial permeability transition, an established mechanism for heart diseases, is a long-standing mystery of mitochondrial biology and a prime drug target for cardioprotection. Several hypotheses about its molecular nature have been put forward over the years, and the prevailing view is that permeabilization of the inner mitochondrial membrane follows opening of a high-conductance channel, the permeability transition pore, which is also called mitochondrial megachannel or multiconductance channel. The permeability transition strictly requires matrix Ca2+ and is favored by the matrix protein cyclophilin D, which mediates the inhibitory effects of cyclosporin A. Here we provide a review of the field, with specific emphasis on the possible role of the adenine nucleotide translocator and of the F-ATP synthase in channel formation, and on currently available small molecule inhibitors. While the possible mechanisms through which the adenine nucleotide translocator and the F-ATP synthase might form high-conductance channels remain unknown, reconstitution experiments and site-directed mutagenesis combined to electrophysiology have provided important clues. The hypothesis that more than one protein may act as a permeability transition pore provides a reasonable explanation for current controversies in the field, and holds great promise for the solution of the mystery of the permeability transition. • The mitochondrial permeability transition (PT) plays a role in heart diseases. • The PT is mediated by inner membrane high-conductance channel(s). • We discuss channel formation by adenine nucleotide translocator and F-ATP synthase. • We review PT inhibitors and their potential use in cardioprotection. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
25. Microbial signature of plaque and gut in acute coronary syndrome.
- Author
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Pisano, Eugenia, Bugli, Francesca, Severino, Anna, Pedicino, Daniela, Paroni Sterbini, Francesco, Martini, Cecilia, De Maio, Flavio, Vinci, Ramona, Sacconi, Andrea, Canonico, Francesco, D'Aiello, Alessia, Bonanni, Alice, Proto, Luca, Ciampi, Pellegrino, Ponzo, Myriana, Grimaldi, Maria Chiara, Urbani, Andrea, Primiano, Aniello, Gervasoni, Jacopo, and Montone, Rocco
- Subjects
- *
ACUTE coronary syndrome , *FISHER discriminant analysis , *TRANSLUMINAL angioplasty , *CARDIOVASCULAR diseases risk factors , *PRINCIPAL components analysis - Abstract
Gut microbiota is an emerging editable cardiovascular risk factor. We aim to investigate gut and coronary plaque microbiota, using fecal samples and angioplasty balloons from patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and control subjects. We examined bacterial communities in gut and coronary plaques by 16S rRNA sequencing and we performed droplet digital PCR analysis to investigate the gut relative abundance of the bacterial genes CutC/CntA involved in trimethylamine N-oxide synthesis. Linear discriminant analysis effect size (LEfSe) at the genus and species levels displayed gut enrichment in Streptococcus, Granulicatella and P. distasonis in ACS compared with CCS and controls; Roseburia, C. aerofaciens and F. prausnitzii were more abundant in controls than in patients. Principal component analysis (PCA) of 41 differentially abundant gut taxa showed a clustering of the three groups. In coronary plaque, LEfSe at the genus level revealed an enrichment of Staphylococcus and Streptococcus in ACS, and Paracoccus in CCS, whereas PCA of 15 differentially abundant plaque taxa exhibited clustering of ACS and CCS patients. CutC and CntA genes were more abundant in ACS and CCS than in controls while no significant difference emerged between ACS and CCS. Our results indicate that ACS and CCS exhibit a different gut and plaque microbial signature, suggesting a possible role of these microbiotas in coronary plaque instability. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
26. Genetic Characterization of a Cohort of Italian Patients with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.
- Author
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Concolino, Paola, Perrucci, Alessia, Carrozza, Cinzia, and Urbani, Andrea
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ADRENOGENITAL syndrome , *GENETIC counseling , *POLYMERASE chain reaction , *GENETIC disorder diagnosis - Abstract
Introduction: Defects in the steroid 21-hydroxylase gene (CYP21A2) cause 21-hydroxylase deficiency (21OHD), the main cause of congenital adrenal hyperplasia (CAH). The disease shows a broad spectrum of clinical forms, ranging from severe or classical (salt wasting, SW, and simple virilizing, SV), to mild late onset or nonclassical (NC). 21OHD affects 1 in 15,000 in its severe classic form and 1 in 200–1000 in its mild NC form. There are many studies reporting the frequency of CYP21A2 pathogenic variants in different populations; however, few of them provide comprehensive information about Italian patients. Here, we present genetic results from a cohort of 245 unrelated Italian individuals with clinical diagnosis of CAH due to 21OHD. Methods: A specific polymerase chain reaction (PCR) protocol combined with Sanger sequencing was used for CYP21A2 analysis. The multiplex ligation-dependent probe amplification (MLPA) assay was employed for copy number variation (CNV) determination. Results: One hundred fourteen (46.5%) of the index cases had the NC form, 57 (23.3%) had the SV form, and 74 (30.2%) presented the SW form of the disease. The most prevalent variant found in NC patients was the p.Val282Leu (51.3%), while the most frequent variants in the classical form were p.Ile173Asn (8.6%) and c.293-13C>G (26.0%). In our study, the frequency of large rearrangements was 15.3%, with CAH-X alleles representing 40% of all DEL/CONV. In addition, 12 alleles carried rare variants, and 1 had a novel variant p.(Arg342Gln). We observed phenotype-genotype correlation in 94.7% of cases. A complete concordance was observed in Groups 0 (enzyme activity completely impaired) where all patients had the SW form as expected. In Group A (0–1% residual enzyme activity), 78.4% of patients had the anticipated SW form while 21.6% were diagnosed with the SV form. Within Group B (~ 2% residual enzyme activity), 93.4% of patients exhibited SV form and 6.5% SW disease. Finally, 92.6% and 7.4% of patients belonging to Group C (enzyme partially impaired to ~ 20–60% residual activity) exhibited NC and SV phenotypes, respectively. Conclusion: This work, representing a comprehensive genetic study, expanded the CYP21A2 variants spectrum of Italian patients with 21OHD and could be helpful in prenatal diagnosis and genetic counseling. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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27. Next-Generation Sequencing for Screening Analysis of Cystic Fibrosis: Spectrum and Novel Variants in a South–Central Italian Cohort.
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De Paolis, Elisa, Tilocca, Bruno, Lombardi, Carla, De Bonis, Maria, Concolino, Paola, Onori, Maria Elisabetta, Ricciardi Tenore, Claudio, Perrucci, Alessia, Roncada, Paola, Capoluongo, Ettore, Urbani, Andrea, Minucci, Angelo, and Santonocito, Concetta
- Subjects
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CYSTIC fibrosis transmembrane conductance regulator , *NUCLEOTIDE sequencing , *CYSTIC fibrosis , *SEQUENCE analysis , *CHLORIDE channels , *PSEUDOMONAS aeruginosa infections - Abstract
The incidence of cystic fibrosis (CF) and the spectrum of cystic fibrosis transmembrane conductance regulator (CFTR) gene variants differ among geographic regions. Differences in CF carrier distribution are also reported among Italian regions. We described the spectrum of the CFTR variants observed in a large group of subjects belonging from central–southern Italy. We also provide a predictive evaluation of the novel variants identified. CFTR screening was performed in a south–central Italian cohort of 770 subjects. We adopted a next-generation sequencing (NGS) approach using the Devyser CFTR NGS kit on the Illumina MiSeq System coupled with Amplicon Suite data analysis. Bioinformatics evaluation of the impact of novel variants was described. Overall, the presence of at least one alternative allele in the CFTR gene was recorded for 23% of the subjects, with a carrier frequency of CF pathogenic variants of 1:12. The largest sub-group corresponded to the heterozygous carriers of a variant with a conflicting interpretation of pathogenicity. The common CFTR p.(Phe508del) pathogenic variants were identified in 37% of mutated subjects. Bioinformatics prediction supported a potential damaging effect for the three novel CFTR variants identified: p.(Leu1187Phe), p.(Pro22Thr), and c.744-3C > G. NGS applied to CF screening had the benefit of: effectively identifying asymptomatic carriers. It lies in a wide overview of CFTR variants and gives a comprehensive picture of the carrier prevalence. The identification of a high number of unclassified variants may represent a challenge whilst at the same time being of interest and relevance for clinicians. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
28. The chitinases as biomarkers in immune-mediate diseases.
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Di Francesco, Angela Maria, Verrecchia, Elena, Manna, Stefano, Urbani, Andrea, and Manna, Raffaele
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MACROPHAGE activation , *BIOMARKERS , *TISSUE remodeling , *LYSOSOMAL storage diseases , *CHITIN , *FOOD pathogens - Abstract
The role of chitinases has been focused as potential biomarkers in a wide number of inflammatory diseases, in monitoring active disease state, and predicting prognosis and response to therapies. The main chitinases, CHIT1 and YKL-40, are derived from 18 glycosyl hydrolases macrophage activation and play important roles in defense against chitin-containing pathogens and in food processing. Moreover, chitinases may have organ- as well as cell-specific effects in the context of infectious diseases and inflammatory disorders and able to induce tissue remodelling. The CHIT1 measurement is an easy, reproducible, reliable, and cost-effective affordable assay. The clinical use of CHIT1 for the screening of lysosomal storage disorders is quite practical, when proper cut-off values are determined for each laboratory. The potential of CHIT1 and chitinases has not been fully explored yet and future studies will produce many surprising discoveries in the immunology and allergology fields of research. However, since the presence of a null CHIT1 gene in a subpopulation would be responsible of false-negative values, the assay should be completed with the other markers such ACE and, if necessary, by genetic analysis when CHIT1 is unexpected low. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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29. Identification and Molecular Characterization of a Novel Large-Scale Variant (Exons 4_18 Loss) in the LDLR Gene as a Cause of Familial Hypercholesterolaemia in an Italian Family.
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Concolino, Paola, De Paolis, Elisa, Moffa, Simona, Onori, Maria Elisabetta, Soldovieri, Laura, Ricciardi Tenore, Claudio, De Bonis, Maria, Rabacchi, Claudio, Santonocito, Concetta, Rinelli, Martina, Calandra, Sebastiano, Giaccari, Andrea, Urbani, Andrea, and Minucci, Angelo
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- *
FAMILIAL hypercholesterolemia , *LIPOPROTEIN receptors , *NUCLEOTIDE sequencing , *MOLECULAR diagnosis , *IDENTIFICATION , *GENES - Abstract
Next-generation sequencing (NGS) is nowadays commonly used for clinical purposes, and represents an efficient approach for the molecular diagnosis of familial hypercholesterolemia (FH). Although the dominant form of the disease is mostly due to the low-density lipoprotein receptor (LDLR) small-scale pathogenic variants, the copy number variations (CNVs) represent the underlying molecular defects in approximately 10% of FH cases. Here, we reported a novel large deletion in the LDLR gene involving exons 4–18, identified by the bioinformatic analysis of NGS data in an Italian family. A long PCR strategy was employed for the breakpoint region analysis where an insertion of six nucleotides (TTCACT) was found. Two Alu sequences, identified within intron 3 and exon 18, could underlie the identified rearrangement by a nonallelic homologous recombination (NAHR) mechanism. NGS proved to be an effective tool suitable for the identification of CNVs, together with small-scale alterations in the FH-related genes. For this purpose, the use and implementation of this cost-effective, efficient molecular approach meets the clinical need for personalized diagnosis in FH cases. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
30. Dual inhibition of CDK12 and CDK13 uncovers actionable vulnerabilities in patient-derived ovarian cancer organoids.
- Author
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Cesari, Eleonora, Ciucci, Alessandra, Pieraccioli, Marco, Caggiano, Cinzia, Nero, Camilla, Bonvissuto, Davide, Sillano, Francesca, Buttarelli, Marianna, Piermattei, Alessia, Loverro, Matteo, Camarda, Floriana, Greco, Viviana, De Bonis, Maria, Minucci, Angelo, Gallo, Daniela, Urbani, Andrea, Vizzielli, Giuseppe, Scambia, Giovanni, and Sette, Claudio
- Abstract
Background: High grade serous ovarian cancer (HGSOC) is highly lethal, partly due to chemotherapy resistance and limited availability of targeted approaches. Cyclin dependent kinases 12 and 13 (CDK12/13) are promising therapeutic targets in human cancers, including HGSOC. Nevertheless, the effects of their inhibition in HGSOC and the potential synergy with other drugs are poorly known. Methods: We analyzed the effects of the CDK12/13 inhibitor THZ531 in HGSOC cells and patient-derived organoids (PDOs). RNA sequencing and quantitative PCR analyses were performed to identify the genome-wide effects of short-term CDK12/13 inhibition on the transcriptome of HGSOC cells. Viability assays with HGSOC cells and PDOs were performed to assess the efficacy of THZ531 as single agent or in combination with clinically relevant drugs. Results: The CDK12 and CDK13 genes are deregulated in HGSOC and their concomitant up-regulation with the oncogene MYC predicts poor prognosis. HGSOC cells and PDOs display high sensitivity to CDK12/13 inhibition, which synergizes with drugs in clinical use for HGSOC. Transcriptome analyses revealed cancer-relevant genes whose expression is repressed by dual CDK12/13 inhibition through impaired splicing. Combined treatment with THZ531 and inhibitors of pathways regulated by these cancer relevant genes (EGFR, RPTOR, ATRIP) exerted synergic effects on HGSOC PDO viability. Conclusions: CDK12 and CDK13 represent valuable therapeutic targets for HGSOC. We uncovered a wide spectrum of CDK12/13 targets as potential therapeutic vulnerabilities for HGSOC. Moreover, our study indicates that CDK12/13 inhibition enhances the efficacy of approved drugs that are already in use for HGSOC or other human cancers. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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31. CSF neuron-specific enolase as a biomarker of neurovascular conflict severity in drug-resistant trigeminal neuralgia: a prospective study in patients submitted to microvascular decompression.
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Baroni, Silvia, Rapisarda, Alessandro, Gentili, Vanessa, Burattini, Benedetta, Moretti, Giacomo, Sarlo, Francesca, Izzo, Alessandro, D'Ercole, Manuela, Olivi, Alessandro, Urbani, Andrea, and Montano, Nicola
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TRIGEMINAL neuralgia , *ENOLASE , *LONGITUDINAL method , *TRIGEMINAL nerve , *PAIN measurement - Abstract
Background: Although neurovascular conflict (NVC) is the most widely accepted cause of trigeminal neuralgia (TN), few articles have analyzed molecular and biochemical mechanisms underlying TN. In the present study, we dosed neuron-specific enolase (NSE) on serum and CSF samples of 20 patients submitted to microvascular decompression (MVD) and correlated these findings with the type of NVC. Methods : Blood samples were obtained preoperatively and 48 h after MVD. CSF from trigeminal cistern was intraoperatively obtained. NSE levels were measured using the Diasorin kit (LIAISON®NSE). NVC was classified as "contact" or "trigeminal nerve distortion/indentation" or "trigeminal root atrophy" based on MRI and intraoperative findings. Clinical outcome was measured by acute pain relief (APR) and Barrow Neurological Institute (BNI) scale at last available follow-up (FU; 6.40 ± 5.38 months). Results: APR was obtained in all patients. A statistically significant BNI reduction was obtained at latest FU (p < 0.0001). Serum NSE levels significantly decreased following MVD (from 12.15 ± 3.02 ng/mL to 8.95 ± 2.83 ng/mL, p = 0.001). The mean CSF NSE value was 48.94 ng/mL, and the mean CSF/serum NSE rate was 4.18 with a strong correlation between these two variables (p = 0.0008). CSF NSE level in "trigeminal root atrophy" group was significantly higher compared to "contact" (p = 0.0045) and "distortion/indentation" (p = 0.010) groups. Conclusion: NSE levels seem to be related to the etiopathology and severity of NVC. A significant reduction of serum NSE levels could be related to the resolution of the NVC and clinical TN improvement. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
32. Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial.
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Calvani, Riccardo, Gervasoni, Jacopo, Picca, Anna, Ciciarello, Francesca, Galluzzo, Vincenzo, Coelho-Júnior, Hélio José, Di Mario, Clara, Gremese, Elisa, Lomuscio, Sara, Paglionico, Anna Maria, Santucci, Lavinia, Tolusso, Barbara, Urbani, Andrea, Marini, Federico, Marzetti, Emanuele, Landi, Francesco, and Tosato, Matteo
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POST-acute COVID-19 syndrome , *VITAMIN C , *CLINICAL trials , *DIETARY supplements , *ARGININE , *COVID-19 - Abstract
Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection. l-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., l-arginine/ADMA, l-arginine/citrulline+ornithine, and l-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS–DA) models were built to characterize systemic l-arginine metabolism and assess the effects of the supplementation. PLS–DA allowed discrimination of participants with long COVID from healthy controls with 80.2 ± 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations and l-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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33. Basophil Activation Test with Different Polyethylene Glycols in Patients with Suspected PEG Hypersensitivity Reactions.
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Vespa, Simone, Del Biondo, Pietro, Simeone, Pasquale, Cavallucci, Enrico, Catitti, Giulia, Auciello, Raffaella, De Bellis, Domenico, Altomare, Isotta, Pierdomenico, Laura, Canonico, Barbara, Cicalini, Ilaria, Angilletta, Ilaria, Del Boccio, Piero, Pieragostino, Damiana, Santilli, Francesca, Urbani, Andrea, De Laurenzi, Vincenzo, Stuppia, Liborio, and Lanuti, Paola
- Subjects
- *
BASOPHILS , *SKIN tests , *DRUG allergy , *ALLERGIES - Abstract
Allergic reactions to COVID-19 vaccine components are rare but should be considered. Polyethylene glycol (PEG) is responsible for anaphylaxis in mRNA vaccines. Skin tests have been used in the allergological work-up programs for COVID-19 vaccine evaluation. However, the reproducibility of the skin prick test is time-dependent and the reactivity declines over time. Therefore, we combined the administration of the skin tests with the basophil activation test (BAT) using PEG2000, PEG4000 and DMG-PEG2000, where the BAT was considered positive when the percentage of activated basophils was higher than 6%, 5% and 6.5%, for PEG 4000, PEG2000 and DMG-PEG2000, respectively. To this end, among the subjects that underwent allergy counseling at the Allergy Unit of our Institution during the 2020/2021 vaccination campaign, 13 patients had a suggested medical history of PEG/drug hypersensitivity and were enrolled together with 10 healthy donors. Among the enrolled patients 2 out of 13 tested patients were positive to the skin test. The BAT was negative in terms of the percentages of activated basophils in all analyzed samples, but the stimulation index (SI) was higher than 2.5 in 4 out of 13 patients. These data evidenced that, when the SI is higher than 2.5, even in the absence of positivity to BAT, the BAT to PEG may be a useful tool to be coupled to skin tests to evidence even low-grade reactions. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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34. The Functional Characteristics of Goat Cheese Microbiota from a One-Health Perspective.
- Author
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Tilocca, Bruno, Soggiu, Alessio, Iavarone, Federica, Greco, Viviana, Putignani, Lorenza, Ristori, Maria Vittoria, Macari, Gabriele, Spina, Anna Antonella, Morittu, Valeria Maria, Ceniti, Carlotta, Piras, Cristian, Bonizzi, Luigi, Britti, Domenico, Urbani, Andrea, Figeys, Daniel, and Roncada, Paola
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GOAT cheese , *GUT microbiome , *GOAT milk , *CHEESE ripening , *MEDITERRANEAN diet , *DAIRY products - Abstract
Goat cheese is an important element of the Mediterranean diet, appreciated for its health-promoting features and unique taste. A pivotal role in the development of these characteristics is attributed to the microbiota and its continuous remodeling over space and time. Nevertheless, no thorough study of the cheese-associated microbiota using two metaomics approaches has previously been conducted. Here, we employed 16S rRNA gene sequencing and metaproteomics to explore the microbiota of a typical raw goat milk cheese at various ripening timepoints and depths of the cheese wheel. The 16S rRNA gene-sequencing and metaproteomics results described a stable microbiota ecology across the selected ripening timepoints, providing evidence for the microbiologically driven fermentation of goat milk products. The important features of the microbiota harbored on the surface and in the core of the cheese mass were highlighted in both compositional and functional terms. We observed the rind microbiota struggling to maintain the biosafety of the cheese through competition mechanisms and/or by preventing the colonization of the cheese by pathobionts of animal or environmental origin. The core microbiota was focused on other biochemical processes, supporting its role in the development of both the health benefits and the pleasant gustatory nuances of goat cheese. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
35. Light Microscopy and Proteomic Patterns of Ovulation in Cervical Mucus.
- Author
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Fernandez-Hermida, Yolanda, Vincenzoni, Federica, Milardi, Domenico, Astorri, Anna Laura, Urbani, Andrea, Grande, Giuseppe, and Azagra, Rafael
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- *
MUCUS , *OVULATION , *PROTEOMICS , *MICROSCOPY , *ELASTASES , *HEAT shock proteins , *MAGNETIC resonance microscopy , *DEFENSINS - Abstract
Three out of the eight proteins that significantly increased their presence on day 18 of the cycle were also identified previously by Grande et al.: small proline-rich protein 3 (SPRR3) and WAP four-disulfide core domain protein 2 (WFDC2) as constitutive proteins, and desmoglein-3 (DSG3) as an ovulatory-specific protein. [Extracted from the article]
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- 2022
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36. Short-Chain Fatty Acids Modulate Sperm Migration through Olfactory Receptor 51E2 Activity.
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Teveroni, Emanuela, Di Nicuolo, Fiorella, Vergani, Edoardo, Bruno, Carmine, Maulucci, Giuseppe, Bianchetti, Giada, Astorri, Anna Laura, Grande, Giuseppe, Gervasoni, Jacopo, Santucci, Lavinia, De Spirito, Marco, Urbani, Andrea, Pontecorvi, Alfredo, Mancini, Francesca, and Milardi, Domenico
- Subjects
- *
SHORT-chain fatty acids , *MALE reproductive organs , *OLFACTORY receptors , *REPRODUCTION , *SPERMATOZOA , *MASS spectrometry , *CONFOCAL microscopy - Abstract
The non-orthotopic expression of olfactory receptors (ORs) includes the male reproductive system, and in particular spermatozoa; their active ligands could be essential to sperm chemotaxis and chemical sperm–oocyte communication. OR51E2 expression has been previously reported on sperm cells' surface. It has been demonstrated in different cellular models that olfactory receptor 51E2 (OR51E2) binds volatile short-chain fatty acids (SCFAs) as specific ligands. In the present research, we make use of Western blot, confocal microscopy colocalization analysis, and the calcium-release assay to demonstrate the activation of sperm cells through OR51E2 upon SCFAs stimulus. Moreover, we perform a novel modified swim-up assay to study the involvement of OR51E2/SCFAs in sperm migration. Taking advantage of computer-assisted sperm analysis (CASA system), we determine the kinematics parameters of sperm cells migrating towards SCFAs-enriched medium, revealing that these ligands are able to promote a more linear sperm-cell orientation. Finally, we obtain SCFAs by mass spectrometry in cervico-vaginal mucus and show for the first time that a direct incubation between cervical mucus and sperm cells could promote their activation. This study can shed light on the possible function of chemosensory receptors in successful reproduction activity, laying the foundation for the development of new strategies for the treatment of infertile individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
37. Integrating a Comprehensive Cancer Genome Profiling into Clinical Practice: A Blueprint in an Italian Referral Center.
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Nero, Camilla, Duranti, Simona, Giacomini, Flavia, Minucci, Angelo, Giacò, Luciano, Piermattei, Alessia, Genuardi, Maurizio, Pasciuto, Tina, Urbani, Andrea, Daniele, Gennaro, Lorusso, Domenica, Pignataro, Raffaele, Tortora, Giampaolo, Normanno, Nicola, and Scambia, Giovanni
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- *
GENOMES , *NANOTECHNOLOGY , *WORKFLOW , *GENE expression profiling - Abstract
The implementation of cancer molecular characterization in clinical practice has improved prognostic re-definition, extending the eligibility to a continuously increasing number of targeted treatments. Broad molecular profiling technologies better than organ-based approaches are believed to serve such dynamic purposes. We here present the workflow our institution adopted to run a comprehensive cancer genome profiling in clinical practice. This article describes the workflow designed to make a comprehensive cancer genome profiling program feasible and sustainable in a large-volume referral hospital. [ABSTRACT FROM AUTHOR]
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- 2022
- Full Text
- View/download PDF
38. A commentary on the discrepancy between blood and tumour BRCA testing: An open question.
- Author
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De Paolis, Elisa, Marchetti, Claudia, Concolino, Paola, Scambia, Giovanni, Urbani, Andrea, Fagotti, Anna, and Minucci, Angelo
- Abstract
Currently, the size of CNA rearrangements range from 50 bp to several Mb; B Tumour I BRCA i (t I BRCA i ) testing b , t I BRCA i testing is the molecular evaluation of I BRCA i genes from tumour tissue, mainly on formalin-fixed paraffin-embedded (FFPE) samples. Reliability of tumor testing compared to germline testing for detecting BRCA1 and BRCA2 mutations in patients with epithelial ovarian cancer. For each reference study, the number of subjects with paired tumour and germline I BRCA i tests is reported, together with the cancer and specimen types. This approach allows the identification of inherited and non-inherited I BRCA i PVs; B Germline I BRCA i (g I BRCA i ) testing b , g I BRCA i testing is the molecular evaluation of I BRCA i genes mainly from blood samples. [Extracted from the article]
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- 2022
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39. Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency.
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Paragliola, Rosa Maria, Perrucci, Alessia, Foca, Laura, Urbani, Andrea, and Concolino, Paola
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ADRENOGENITAL syndrome , *EHLERS-Danlos syndrome , *HUMAN genome , *SYMPTOMS , *GENETIC variation , *SYNDROMES - Abstract
21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in CYP21A2 gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The CYP21A2 gene is located on the long arm of chromosome 6, within the RCCX region, one of the most complex loci in the human genome. The 3′untranslated sequence of CYP21A2 exon 10 overlap the last exon of TNXB gene (these genes lie on the opposite strands of DNA and have the opposite transcriptional direction) that encodes an extracellular matrix glycoprotein tenascin-X (TNX). A recombination event between TNXB and its pseudogene TNXA causes a 30 kb deletion producing a chimeric TNXA/TNXB gene (CAH-X chimera) where both CYP21A2 and TNXB genes are impaired. This genetic condition characterizes a subset of patients with 21OHD who display the hypermobility phenotype of Ehlers–Danlos syndrome (hEDS) (CAH-X Syndrome). The aim of this study was to assess the prevalence of CAH-X syndrome in an Italian cohort of patients with 21OHD. At this purpose, 196 probands were recruited. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were used to identify the CAH-X genotype. Twenty-one individuals showed the heterozygous continuous deletion involving the CYP21A2 and part of the TNXB gene. EDS-related clinical manifestations were identified in most patients carrying the CAH-X chimera. A CAH-X prevalence of 10.7% was estimated in our population. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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40. The role of biomarkers in drug-resistant trigeminal neuralgia: a prospective study in patients submitted to surgical treatment.
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Rapisarda, Alessandro, Baroni, Silvia, Gentili, Vanessa, Moretti, Giacomo, Burattini, Benedetta, Sarlo, Francesca, Olivi, Alessandro, Urbani, Andrea, and Montano, Nicola
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TRIGEMINAL neuralgia , *LONGITUDINAL method , *BIOMARKERS , *URIC acid , *ANALGESIA - Abstract
Background: Molecular mechanisms underlying trigeminal neuralgia (TN) have been poorly understood. Recently, different biomarkers have been studied in several chronic neuropathic diseases or in neuronal damage, but their role in TN has not yet been investigated. Here, we firstly analyzed the serum levels of the neuron-specific enolase (NSE) (as an index of neuronal tissue damage) in TN patients submitted to surgical treatment. Different cytokines and interleukins related to inflammation were also studied. Methods: Blood samples from 40 patients were prospectively collected preoperatively and after the surgical procedure, namely microvascular decompression (MVD) and percutaneous balloon compression (PBC). Serum levels of uric acid, NSE, ferritin, CRP, IL-2R, and IL-6 were studied. The acute pain relief (APR) and the pre- and postoperative BNI were used to evaluate the clinical outcome. Results: Overall, we obtained an APR in 87.5% of patients and a significant reduction of BNI after surgery (p < 0.0001). We observed a significant reduction of postoperative NSE values in the group of patients undergoing MVD (p = 0.0055) and a significant increase of postoperative NSE values in patients undergoing PBC (p < 0.05). Furthermore, in the group of patients undergoing MVD, we found a significant postoperative increase of CRP (p < 0.0001), ferritin (p = 0.001), and IL-6 (p = 0.01) values. The only patient who did not respond to MVD had NSE levels unchanged. Conclusion: Our results suggest the hypothesis that TN would be related to the neural damage instead of the systemic inflammatory status and indicate NSE as a possible biomarker of response in patients submitted to MVD. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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41. Genetics and Sport Injuries: New Perspectives for Athletic Excellence in an Italian Court of Rugby Union Players.
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Onori, Maria Elisabetta, Pasqualetti, Massimo, Moretti, Giacomo, Canu, Giulia, De Paolis, Giulio, Baroni, Silvia, Minucci, Angelo, Galvani, Christel, and Urbani, Andrea
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RUGBY football players , *SPORTS injuries , *GENETICS , *BONE injuries , *ATHLETIC ability , *PHENOTYPES - Abstract
Several genes are involved in sport performance, especially in injuries incidence. The aim of this study was to investigate the association of ACE, ACTN3, COL1A1, and MCT1 genotypes and injuries in rugby players in order to find a genotype/phenotype correlation and provide useful information improving athletic performance. One-hundred male professional and semiprofessional rugby players were selected. Analysis was performed genotyping the genes ACE, ACTN3, COL1A1, and MCT1 as candidate gene of interest involved in athletic performance. A control group of non-athletic Italian male participants was analyzed to compare the results. We found statistical significance of MCT1 rs1049434 AA for total injuries (χ2 = 0.115; p = 0.003) and bone injuries (χ2 = 0.603; p = 0.007) in the rugby athlete population. No statistical significance was found between injury incidence and ACE, ACTN3, COL1A1 genotypes. The MCT1 AA genotype is associated with the incidence of total and bone injuries in the rugby player population. Although environmental factors such as lifestyle, diet, training, and stress can influence athletic performance, our data demonstrated the importance of genetic study in sport aimed at developing personalized training and achieving the best possible athletic excellence. [ABSTRACT FROM AUTHOR]
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- 2022
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42. The Relationship between ACE , ACTN3 and MCT1 Genetic Polymorphisms and Athletic Performance in Elite Rugby Union Players: A Preliminary Study.
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Pasqualetti, Massimo, Onori, Maria Elisabetta, Canu, Giulia, Moretti, Giacomo, Minucci, Angelo, Baroni, Silvia, Mordente, Alvaro, Urbani, Andrea, and Galvani, Christel
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ELITE athletes , *RUGBY football players , *ATHLETIC ability , *AEROBIC capacity , *MONOCARBOXYLATE transporters , *GENETIC polymorphisms , *ANGIOTENSIN converting enzyme - Abstract
Athletic performance is influenced by many factors such as the environment, diet, training and endurance or speed in physical effort and by genetic predisposition. Just a few studies have analyzed the impact of genotypes on physical performance in rugby. The aim of this study was to verify the modulation of genetic influence on rugby-specific physical performance. Twenty-seven elite rugby union players were involved in the study during the in-season phase. Molecular genotyping was performed for: angiotensin-converting enzyme (ACE rs4646994), alfa-actinin-3 (ACTN3 rs1815739) and monocarboxylate transporter 1 (MCT1 rs1049434) and their variants. Lean mass index (from skinfolds), lower-limb explosive power (countermovement jump), agility (505), speed (20 m), maximal aerobic power (Yo-yo intermittent recovery test level 1) and repeated sprint ability (12 × 20 m) were evaluated. In our rugby union players ACE and ACTN3 variants did not show any influence on athletic performance. MCT1 analysis showed that TT-variant players had the highest peak vertical power (p = 0.037) while the ones with the AA genotype were the fastest in both agility and sprint tests (p = 0.006 and p = 0.012, respectively). Considering the T-dominant model, the AA genotype remains the fastest in both tests (agility: p = 0.013, speed: p = 0.017). Only the MCT1 rs1049434 A allele seems to be advantageous for elite rugby union players, particularly when power and speed are required. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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43. Intestinal Permeability and Dysbiosis in Female Patients with Recurrent Cystitis: A Pilot Study.
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Graziani, Cristina, Laterza, Lucrezia, Talocco, Claudia, Pizzoferrato, Marco, Di Simone, Nicoletta, D'Ippolito, Silvia, Ricci, Caterina, Gervasoni, Jacopo, Persichilli, Silvia, Del Chierico, Federica, Marzano, Valeria, Mortera, Stefano Levi, Primiano, Aniello, Poscia, Andrea, Ponziani, Francesca Romana, Putignani, Lorenza, Urbani, Andrea, Petito, Valentina, Di Vincenzo, Federica, and Masi, Letizia
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GUT microbiome , *INTESTINAL physiology , *WOMEN patients , *CYSTITIS , *URINARY tract infections , *DYSBIOSIS , *RECURRENT miscarriage , *PERMEABILITY - Abstract
Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most frequently by Escherichia coli. Intestinal contiguity contributes to the etiopathogenesis of RC and an alteration in intestinal permeability could have a major role in RC. The aim of this pilot study is to assess gut microbiome dysbiosis and intestinal permeability in female patients with RC. Patients with RC (n = 16) were enrolled and compared with healthy female subjects (n = 15) and patients with chronic gastrointestinal (GI) disorders (n = 238). We calculated the Acute Cystitis Symptom Score/Urinary Tract Infection Symptom Assessment (ACSS/UTISA) and Gastrointestinal Symptom Rating Scale (GSRS) scores and evaluated intestinal permeability and the fecal microbiome in the first two cohorts. Patients with RC showed an increased prevalence of gastrointestinal symptoms compared with healthy controls. Of the patients with RC, 88% showed an increased intestinal permeability with reduced biodiversity of gut microbiota compared to healthy controls, and 68% of the RC patients had a final diagnosis of gastrointestinal disease. Similarly, GI patients reported a higher incidence of urinary symptoms with a diagnosis of RC in 20%. Gut barrier impairment seems to play a major role in the pathogenesis of RC. Further studies are necessary to elucidate the role of microbiota and intestinal permeability in urinary tract infections. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
44. Multispot multiphoton Ca2+ imaging in acute myocardial slices.
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Borile, Giulia, de Mauro, Claudio, Urbani, Andrea, Alfieri, Domenico, Pavone, Francesco S., and Mongillo, Marco
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MULTIPHOTON spectroscopy , *CALCIUM , *HEART , *TISSUES , *SPECTROMETRY , *LASER beams - Abstract
Multiphoton microscopy has become essential for dynamic imaging in thick living tissues. High-rate, full-field image acquisition in multiphoton microscopy is achievable by parallelization of the excitation and detection pathways. We developed our approach via a diffractive optical element which splits a pulsed laser into 16 beamlets and exploits a descanned detection system consisting of an array of beamlet-associated photomultiplier tubes. The optical performance of the multiphoton multispot system (MCube) has been characterized in cardiac tissue sections and subsequently used for the first time for fluorescence imaging of cardiomyocyte Ca2+ dynamics in viable acute cardiac slices. Multispot multiphoton microscopy (MMM) has never been used before to monitor Ca2+ dynamics in thick, viable tissue samples. Acute heart slices are a powerful close-to-in vivo model of Ca2+ imaging allowing the simultaneous observation of several cells in their own tissue environment, exploiting the multiphoton excitation ability to penetrate scattering tissues. Moreover, we show that the concurrent high spatial and temporal resolutions afforded by the parallel scanning in MMM can be exploited to simultaneously assess subcellular Ca2+ dynamics in different cells in the tissue. We recorded local Ca2+ release events including macrosparks, travelling waves, and rotors. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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45. Repurposing of Trimetazidine for amyotrophic lateral sclerosis: A study in SOD1G93A mice.
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Scaricamazza, Silvia, Salvatori, Illari, Amadio, Susanna, Nesci, Valentina, Torcinaro, Alessio, Giacovazzo, Giacomo, Primiano, Aniello, Gloriani, Michela, Candelise, Niccolò, Pieroni, Luisa, Loeffler, Jean‐Philippe, Renè, Frederique, Quessada, Cyril, Tefera, Tesfaye W., Wang, Hao, Steyn, Frederik J., Ngo, Shyuan T., Dobrowolny, Gabriella, Lepore, Elisa, and Urbani, Andrea
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MOTOR neuron diseases , *AMYOTROPHIC lateral sclerosis , *TRIMETAZIDINE , *MOTOR neurons , *SPINAL nerves , *PERIPHERAL nervous system - Abstract
Background and Purpose: Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by the degeneration of upper and lower motor neurons, progressive wasting and paralysis of voluntary muscles and is currently incurable. Although considered to be a pure motor neuron disease, increasing evidence indicates that the sole protection of motor neurons by a single targeted drug is not sufficient to improve the pathological phenotype. We therefore evaluated the therapeutic potential of the multi‐target drug used to treatment of coronary artery disease, trimetazidine, in SOD1G93A mice. Experimental Approach As a metabolic modulator, trimetazidine improves glucose metabolism. Furthermore, trimetazidine enhances mitochondrial metabolism and promotes nerve regeneration, exerting an anti‐inflammatory and antioxidant effect. We orally treated SOD1G93A mice with trimetazidine, solubilized in drinking water at a dose of 20 mg kg−1, from disease onset. We assessed the impact of trimetazidine on disease progression by studying metabolic parameters, grip strength and histological alterations in skeletal muscle, peripheral nerves and the spinal cord. Key Results: Trimetazidine administration delays motor function decline, improves muscle performance and metabolism, and significantly extends overall survival of SOD1G93A mice (increased median survival of 16 days and 12.5 days for male and female respectively). Moreover, trimetazidine prevents the degeneration of neuromuscular junctions, attenuates motor neuron loss and reduces neuroinflammation in the spinal cord and in peripheral nerves. Conclusion and Implications: In SOD1G93A mice, therapeutic effect of trimetazidine is underpinned by its action on mitochondrial function in skeletal muscle and spinal cord. [ABSTRACT FROM AUTHOR]
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- 2022
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46. Ceramic-on-metal coupling in THA: long term clinical and radiographic outcomes using two different short stems.
- Author
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Logroscino, Giandomenico, Saracco, Michela, Maccauro, Giulio, Urbani, Andrea, Ciavardelli, Domenico, Consalvo, Ada, Ferraro, Daniele, and Falez, Francesco
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TOTAL hip replacement , *CHROMIUM ions , *HIP osteoarthritis , *ION analysis , *ADHESIVE wear , *REOPERATION , *COBALT , *ARTIFICIAL joints , *BIOMEDICAL materials , *PROSTHESIS design & construction , *LONGITUDINAL method ,RESEARCH evaluation - Abstract
Background: Hip prosthetic replacement surgery is the gold standard for patients affected by symptomatic osteoarthritis. The ceramic-on-metal hybrid hard-on-hard bearing was initially launched on the market with the purpose of reducing adhesive and corrosion wear, loss of metal debris and ions and risk of fracture and squeaking. However, this bearing was withdrawn from the market, in the apprehension of local and systemic toxicity. The aim of this study is to evaluate the reliability and safety of ceramic-on-metal bearing at long term follow-up.Methods: From 2 cohorts of patients suffering of hip osteoarthritis who underwent total hip arthroplasty using ceramic-on-metal bearing with two different short stems, 19 of the GROUP A and 25 of the GROUP B were suitable for this study. All patients were compared clinically using the Harris Hip Score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS), 12-item Short Form Health Survey (SF12P/M), and radiographically. Blood samples were collected in order to evaluate chromium and cobalt ions level. The two groups were compared in terms of metal ions blood levels, and finally all the implanted prostheses were compared with a healthy control group.Results: All the implanted stems were well-positioned and osseointegrated at a mean follow-up of 114 months. Improvements were observed for all clinical scores comparing preoperative and postoperative values in both groups. Radiographic evaluation showed a good ability to restore proper articular geometry. Chromium and cobalt ion analysis revealed values below the safety threshold except for 1 case in GROUP A (cup malposition) and 2 cases in GROUP B (6.1%). No revision occurred.Conclusions: Ceramic-on-metal bearing is safe and reliable at long term follow-up in association to short stems arthroplasty, if the implant is correctly positioned. Chromium and cobalt metal ions blood levels evaluation should be performed annually. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
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47. COVID-19 response: effectiveness of weekly rapid risk assessments, Italy.
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Riccardo, Flavia, Guzzetta, Giorgio, Urdiales, Alberto Mateo, Del Manso, Martina, Andrianou, Xanthi D., Bella, Antonino, Pezzotti, Patrizio, Carbone, Simona, De Vito, Tiziana, Maraglino, Francesco, Demicheli, Vittorio, Dario, Claudio, Coscioni, Enrico, Rezza, Giovanni, Urbani, Andrea, Merler, Stefano, and Brusaferro, Silvio
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PUBLIC health surveillance , *PREVENTION of communicable diseases , *RULES , *PUBLIC administration , *RISK assessment , *EMERGENCY management , *INFECTIOUS disease transmission , *COMMUNICATION , *DECISION making , *COVID-19 pandemic - Abstract
Problem After Italy's first national restriction measures in 2020, a robust approach was needed to monitor the emerging epidemic of coronavirus disease 2019 (COVID-19) at subnational level and provide data to inform the strengthening or easing of epidemic control measures. Approach We adapted the European Centre for Disease Prevention and Control rapid risk assessment tool by including quantitative and qualitative indicators from existing national surveillance systems. We defined COVID-19 risk as a combination of the probability of uncontrolled transmission of severe acute respiratory syndrome coronavirus 2 and of an unsustainable impact of COVID-19 cases on hospital services, adjusted in relation to the health system's resilience. The monitoring system was implemented with no additional cost in May 2020. Local setting The infectious diseases surveillance system in Italy uses consistent data collection methods across the country's decentralized regions and autonomous provinces. Relevant changes Weekly risk assessments using this approach were sustainable in monitoring the epidemic at regional level from 4 May 2020 to 24 September 2021. The tool provided reliable assessments of when and where a rapid increase in demand for health-care services would occur if control or mitigation measures were not increased in the following 3 weeks. Lessons learnt Although the system worked well, framing the risk assessment tool in a legal decree hampered its flexibility, as indicators could not be changed without changing the law. The relative complexity of the tool, the impossibility of real-time validation and its use for the definition of restrictions posed communication challenges. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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48. Subclinical autonomic dysfunction in spinobulbar muscular atrophy (Kennedy disease).
- Author
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Rocchi, Camilla, Greco, Viviana, Urbani, Andrea, Di Giorgio, Alessandra, Priori, Marina, Massa, Roberto, Bernardi, Giorgio, and Marfia, Girolama A.
- Abstract
Introduction: Spinobulbar muscular atrophy (SBMA) is an inherited adult-onset motor neuron disease caused by the expansion of a polyglutamine tract within the androgen receptor. Autonomic nervous system involvement (ANS) is not considered part of SBMA. The aim of this study was to assess autonomic cardiovascular function in 5 SBMA patients. Methods: Five quantitative autonomic function tests (AFTs) were performed in 5 SBMA patients. Plasma noradrenaline (NA) concentration in patients and in 5 healthy subjects was also measured. Results: AFTs were abnormal in 4 of the 5 patients, and plasma NA concentration was significantly reduced in patients with respect to controls. Conclusion: The impairment of cardiovascular responses to AFTs in addition to reduced plasma NA concentration observed in our patients suggests subclinical involvement of the ANS in Kennedy disease. Muscle Nerve, 2011 [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
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49. Prevalence and characteristics of myocardial injury during COVID-19 pandemic: A new role for high-sensitive troponin.
- Author
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Maino, Alessandro, Di Stasio, Enrico, Grimaldi, Maria Chiara, Cappannoli, Luigi, Rocco, Erica, Vergallo, Rocco, Biscetti, Federico, Baroni, Silvia, Urbani, Andrea, Landolfi, Raffaele, and Biasucci, Luigi Marzio
- Subjects
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COVID-19 pandemic , *COVID-19 , *TROPONIN , *MYOCARDIAL injury , *TROPONIN I - Abstract
Coronavirus disease 2019 (COVID-19) is a pandemic disease that is causing a public health emergency. Characteristics and clinical significance of myocardial injury remain unclear. This retrospective single-center study analyzed 189 patients who received a COVID-19 diagnosis out of all 758 subjects with a high sensitive troponin I (Hs-TnI) measurement within the first 24 h of admission at the Policlinico A.Gemelli (Rome, Italy) between February 20th 2020 to April 09th 2020. The prevalence of myocardial injury in our COVID-19 population is of 16%. The patients with cardiac injury were older, had a greater number of cardiovascular comorbidities and higher values of acute phase and inflammatory markers and leucocytes. They required more frequently hospitalization in Intensive Care Unit (10 [32.3%] vs 18 [11.4%]; p =.003) and the mortality rate was significantly higher (17 [54.8%] vs. 15 [9.5%], p <.001). Among patients in ICU, the subjects with myocardial injury showed an increase need of endotracheal intubation (8 out of 9 [88%] vs 7 out of 19[37%], p =.042). Multivariate analyses showed that hs-TnI can significantly predict the degree of COVID-19 disease, the intubation need and in-hospital mortality. In this study we demonstrate that hs-Tn can significantly predict disease severity, intubation need and in-hospital death. Therefore, it may be reasonable to use Hs-Tn as a clinical tool in COVID-19 patients in order to triage them into different risk groups and can play a pivotal role in the detection of subjects at high risk of cardiac impairment during both the early and recovery stage. • Prevalence of myocardial injury in COVID-19 population is about 16%. • Patients with myocardial injury were older and with more cardiovascular comorbidities. • Multivariate analyses showed that high-sensitive troponin can predict the degree of COVID-19, intubation need and mortality. • High-sensitive troponin (hs-Tn) can be a clinical tool in COVID-19 patients to triage them into distinct risk groups. • Hs-Tn can play a pivotal role in the detection of subjects at high risk of both short- and long-term cardiac impairment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
50. Sigma-class glutathione transferase from Xenopus laevis: molecular cloning, expression, and site-directed mutagenesis
- Author
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Carletti, Erminia, Luca, Antonella De, Urbani, Andrea, Sacchetta, Paolo, and Ilio, Carmine Di
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GENES , *GLUTATHIONE , *XENOPUS laevis , *NUCLEOTIDES - Abstract
The structural gene for glutathione transferase (XlGSTS1-1) in the amphibia Xenopus laevis has been cloned from an embryo library and its nucleotide sequence has been determined. Open reading frame analysis indicated that xlgsts1 gene encodes the smallest protein of sigma class GST so far identified as being composed of only 194 amino acid residues. The recombinant XlGSTS1-1 shows a narrow range of substrate specificity as well as a significantly lower 1-chloro-2,4-dinitrobenzene conjugation capacity than that of squid sigma class GST. To compare the structural and functional differences between the squid and amphibian enzymes, several site-specific mutations were introduced in XlGSTS1-1, i.e., Ser100Asn, Phe102Tyr, Trp143Leu, Phe146Leu, and Trp148Cys. The results obtained indicate that Trp143 and Trp148 are more important determinants for the structural stability of XlGSTS1-1 rather than for its substrate specificity. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
- View/download PDF
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