1,891 results on '"Napoli"'
Search Results
2. A new solid-phase synthesis of oligonucleotides 3'-conjugated with peptides.
- Author
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De Napoli L, Messere A, Montesarchio D, Piccialli G, Benedetti E, Bucci E, and Rossi F
- Subjects
- HIV-1 drug effects, Magnetic Resonance Spectroscopy, Models, Chemical, Temperature, Chemistry methods, Oligonucleotides chemical synthesis, Peptide Biosynthesis
- Abstract
A convenient 'on line' solid-phase synthesis of oligonucleotides conjugated at the 3'-end with peptides by means of a polymeric support linking the first nucleoside via the base has been developed. A 17-mer designed for antisense experiments against HIV-1, linking at the 3'-terminus the tripeptide Gly-Gly-His, was prepared in good yields and characterized by MALDI-TOF mass spectrometry.
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- 1999
- Full Text
- View/download PDF
3. PROLANG: an expandable software in protein chemistry.
- Author
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Petrilli P, Caporale C, and Sepe C
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- Chemical Phenomena, Chemistry, Proteins, Software
- Abstract
PROLANG is an improved version of the PROSOFT program. Improvements to the old commands were made and new ones were added, PROLANG is an open software that users with BASIC programming experience can easily expand.
- Published
- 1990
- Full Text
- View/download PDF
4. Chemo-physical properties of asbestos bodies in human lung tissues studied at the nano-scale by non-invasive, label free x-ray imaging and spectroscopic techniques
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Francesco Brun, Arianna Di Napoli, Simone De Panfilis, Peter Cloetens, Fabrizio Bardelli, Donata Bellis, Elena Belluso, Silvana Capella, Alessia Cedola, Bardelli, F., Brun, F., De Panfilis, S., Cloetens, P., Capella, S., Belluso, E., Bellis, D., Di Napoli, A., and Cedola, A.
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Male ,0301 basic medicine ,asbestos ,imaging ,lungs ,spectroscopy ,synchrotron radiation ,tomography ,x-ray fluorescence ,X-ray fluorescence ,Asbesto ,Toxicology ,medicine.disease_cause ,Asbestos ,Fluorescence spectroscopy ,Imaging ,03 medical and health sciences ,0302 clinical medicine ,Chrysotile ,medicine ,Humans ,Sample preparation ,Fiber ,Spectroscopy ,Lung ,Tomography ,Aged, 80 and over ,Synchrotron radiation ,Tomography, X-Ray ,Chemistry ,General Medicine ,Spectrometry, Fluorescence ,030104 developmental biology ,Chemical engineering ,Elemental analysis ,Asbestosis ,Female ,Lungs ,030217 neurology & neurosurgery - Abstract
In the lungs, asbestos develops an Fe-rich coating (Asbestos Body, AB) that becomes the actual interface between the foreign fibers and the host organism. Conventional approaches to study ABs require an invasive sample preparation that can alter them. In this work, a novel combination of x-ray tomography and spectroscopy allowed studying unaltered lung tissue samples with chrysotile and crocidolite asbestos. The thickness and mass density maps of the ABs obtained by x-ray tomography were used to derive a truly quantitative elemental analysis from scanning x-ray fluorescence spectroscopy data. The average mass density of the ABs is compatible with that of highly loaded ferritin, or hemosiderin. The composition of all ABs analyzed was similar, with only minor differences in the relative elemental fractions. Silicon concentration decreased in the core-to-rim direction, indicating a possible partial dissolution of the inner fiber. The Fe content in the ABs was higher than that possibly contained in chrysotile and crocidolite. This finding opens two opposite scenarios, the first with Fe coming from the fiber bulk and concentrating on the surface as long as the fiber dissolves, the second where the Fe that takes part to the formation of the AB originates from the host organism Fe-pool.
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- 2021
5. Lipid Accumulation in Hearts Transplanted From Nondiabetic Donors to Diabetic Recipients
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Cristiano Amarelli, Paolo Golino, Gelsomina Mansueto, Michele D'Amico, Ciro Maiello, Claudio Napoli, Salvatore Esposito, Irene Mattucci, Nunzia D'Onofrio, Giuseppe Paolisso, Maria Luisa Balestrieri, Raffaele Marfella, Marisa De Feo, Francesco Cacciatore, Gemma Salerno, Marfella, Raffaele, Amarelli, Cristiano, Cacciatore, Francesco, Balestrieri, Maria Luisa, Mansueto, Gelsomina, D'Onofrio, Nunzia, Esposito, Salvatore, Mattucci, Irene, Salerno, Gemma, De Feo, Marisa, D'Amico, Michele, Golino, Paolo, Maiello, Ciro, Paolisso, Giuseppe, Napoli, Claudio, Marfella, R., Amarelli, C., Cacciatore, F., Balestrieri, M. L., Mansueto, G., D'Onofrio, N., Esposito, S., Mattucci, I., Salerno, G., De Feo, M., D'Amico, M., Golino, P., Maiello, C., Paolisso, G., and Napoli, C.
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Male ,medicine.medical_specialty ,Diabetic Cardiomyopathies ,Heart Ventricles ,medicine.medical_treatment ,Context (language use) ,030204 cardiovascular system & hematology ,heart transplantation ,Gastroenterology ,Follow-Up Studie ,Heart Ventricle ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,DMCM ,Diabetic cardiomyopathy ,diabetic cardiomyopathy ,medicine ,Humans ,Hypoglycemic Agents ,Myocytes, Cardiac ,Prospective Studies ,030212 general & internal medicine ,Diabetic Cardiomyopathie ,Heart Failure ,Heart transplantation ,Hypoglycemic Agent ,business.industry ,Middle Aged ,CVD ,Lipid Metabolism ,medicine.disease ,Metformin ,Prospective Studie ,Diabetes Mellitus, Type 2 ,Lipotoxicity ,chemistry ,diabete ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,Human ,medicine.drug - Abstract
Background: Early pathogenesis of diabetic cardiomyopathy (DMCM) may involve lipotoxicity of cardiomyocytes in the context of hyperglycemia. There are many preclinical studies of DMCM pathogenesis, but the human evidence is still poorly understood. Objectives: By using a nondiabetic mellitus (non-DM) heart transplanted (HTX) in diabetes mellitus (DM) recipients, this study conducted a serial study of human heart transplant recipients evaluating cardiac effects of diabetic milieu (hyperglycemia and insulin resistance) on lipotoxic-mediated injury. We evaluated cardiomyocyte morpho-pathology by seriated biopsies of healthy implanted hearts in DM recipients during 12-month follow-up from HTX. Because metformin reduces ectopic lipid accumulation, we evaluated the effects of the drug in a nonrandomized subgroup. Methods: The DMCM-AHEAD (Diabetes and Lipid Accumulation and Heart Transplant) prospective ongoing study (NCT03546062) evaluated 158 first HTX recipients (82 non-DM, 76 DM of whom 35 [46%] were receiving metformin). HTX recipients were undergoing clinical standard evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsies). Biopsies evaluated immune response, Oil Red-O staining, ceramide, and triacylglycerol levels. Lipotoxic factors and insulin resistance were evaluated by reverse transcriptase–polymerase chain reaction. Results: There was a significant early and progressive cardiomyocyte lipid accumulation in DM but not in non-DM recipients (p = 0.019). In the subgroup receiving metformin, independently from immunosuppressive therapy that was similar among groups, lipid accumulation was reduced in comparison with DM recipients not receiving the drug (hazard ratio: 6.597; 95% confidence interval: 2.516 to 17.296; p < 0.001). Accordingly, lipotoxic factors were increased in DM versus non-DM recipients, and, relevantly, metformin use was associated with fewer lipotoxic factors. Conclusions: Early pathogenesis of human DMCM started with cardiomyocyte lipid accumulation following HTX in DM recipients. Metformin use was associated with reduced lipid accumulation independently of immunosuppressive therapy. This may constitute a novel target for therapy of DMCM.
- Published
- 2020
6. Novel Insights Regarding Nitric Oxide and Cardiovascular Diseases
- Author
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Claudio Napoli, Teresa Infante, Dario Costa, Infante, T., Costa, D., and Napoli, C.
- Subjects
Vascular smooth muscle ,Phosphodiesterase Inhibitors ,Sildenafil ,heart failure ,Vasodilation ,Vascular Remodeling ,030204 cardiovascular system & hematology ,Pharmacology ,Nitric Oxide ,Cardiovascular System ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,atherosclerosi ,Soluble Guanylyl Cyclase ,0302 clinical medicine ,pulmonary arterial hypertension ,medicine ,Animals ,Humans ,Nitric Oxide Donors ,coronary heart disease ,Cyclic GMP ,030304 developmental biology ,0303 health sciences ,Ejection fraction ,business.industry ,Hemodynamics ,systemic hypertension ,Tetrahydrobiopterin ,medicine.disease ,Tadalafil ,chemistry ,Cardiovascular Diseases ,Heart failure ,Cardiology and Cardiovascular Medicine ,business ,Oxidation-Reduction ,Signal Transduction ,medicine.drug - Abstract
Nitric oxide (NO) is a powerful mediator with biological activities such as vasodilation and prevention of vascular smooth muscle cell proliferation as well as functional regulation of cardiac cells. Thus, impaired production or reduced bioavailability of NO predisposes to the onset of different cardiovascular (CV) diseases. Alterations in the redox balance associated with excitation–contraction coupling have been identified in heart failure (HF), thus contributing to contractile abnormalities and arrhythmias. For its ability to influence cell proliferation and angiogenesis, NO may be considered a therapeutic option for the management of several CV diseases. Several clinical studies and trials investigated therapeutic NO strategies for systemic hypertension, atherosclerosis, and/or prevention of in stent restenosis, coronary heart disease (CHD), pulmonary arterial hypertension (PAH), and HF, although with mixed results in long-term treatment and effective dose administered in selected groups of patients. Tadalafil, sildenafil, and cinaguat were evaluated for the treatment of PAH, whereas vericiguat was investigated in the treatment of HF patients with reduced ejection fraction. Furthermore, supplementation with hydrogen sulfide, tetrahydrobiopterin, and nitrite/nitrate has shown beneficial effects at the vascular level.
- Published
- 2021
7. Calcium daily intake and the efficacy of a training intervention on optimizing calcium supplementation therapy: A clinical audit
- Author
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Raffaele Giannettino, Massimo Maddaloni, Carolina Sepe, Antonietta Scognamiglio, Giovanni Mansueto, Federica Coretti, Giovanni Paudice, Riccardo Muscariello, Salvatore Falanga, Elisabetta Palermo, Vincenzo D’Anna, Giovanni Napoli, Vincenzo Ruocco, Simone De Vita, Salvatore Scognamiglio, Ornella Romano, Giuseppe Bruno, Serena Ippolito, Michele Adolfo, Vincenzo Nuzzo, Domenico Rendina, Enrico Benedetto, Patrizia Parente, Maria Rosaria Martino, Paolo Peluso, Muscariello, Riccardo, Rendina, Domenico, Giannettino, Raffaele, Ippolito, Serena, Romano, Ornella, Coretti, Federica, De Vita, Simone, Martino, Maria Rosaria, Sepe, Carolina, Nuzzo, Vincenzo, Adolfo, Michele, Benedetto, Enrico, Bruno, Giuseppe, D’Anna, Vincenzo, Falanga, Salvatore, Maddaloni, Massimo, Mansueto, Giovanni, Napoli, Giovanni, Palermo, Elisabetta, Parente, Patrizia, Paudice, Giovanni, Peluso, Paolo, Ruocco, Vincenzo, Scognamiglio, Antonietta, and Scognamiglio, Salvatore
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Adult ,Male ,Clinical audit ,Health Knowledge, Attitudes, Practice ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Training intervention ,education ,Population ,Medicine (miscellaneous) ,chemistry.chemical_element ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Calcium ,Recommended Dietary Allowances ,Drug Prescriptions ,03 medical and health sciences ,0302 clinical medicine ,Calcium supplementation ,General Practitioners ,Intervention (counseling) ,Internal medicine ,Vitamin D and neurology ,Humans ,Medicine ,Practice Patterns, Physicians' ,Medical prescription ,Aged ,Medical Audit ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,Feeding Behavior ,Middle Aged ,Drug Utilization ,Calcium, Dietary ,Italy ,chemistry ,Dietary Supplements ,Education, Medical, Continuing ,Female ,Diet, Healthy ,Cardiology and Cardiovascular Medicine ,business - Abstract
Calcium is an essential element for human health, with key roles in the prevention and therapy of multifactorial conditions. Calcium dietary intake is often insufficient in the general population. The aim of this study was to perform a clinical audit for general practitioners (GPs) to understand the efficacy of training intervention on doctors' awareness about dietary calcium and supplements.General practice outpatients were enrolled (Before Clinical Audit, BCA) from the same sanitary district, and calcium dietary intake was evaluated with a validated questionnaire, also collecting information about the consumption of calcium and vitamin D supplements. Then, a training intervention with a frontal lesson and discussion with GPs involved was performed. After one month of this intervention, a second outpatient enrolment was performed (Post Clinical Audit, PCA) in the same general practices to evaluate differences in nutritional suggestions and supplement prescription by GPs. In BCA, the calcium dietary intake was low, with nobody reaching 1000 mg as suggested by the guidelines. Only 6.6% and 24.5% took calcium and vitamin D supplements, respectively; in the PCA, these percentages increased to 28% and 78% for calcium and vitamin D supplements, respectively (p 0.01 PCA vs BCA). There were no differences in calcium dietary intake between BCA and PCA.Training intervention on GPs was successful to sensitize them regarding calcium intake problems; GPs tended to increase the prescription of supplements but not to suggest changes in dietary habits.
- Published
- 2021
8. Epigenetic susceptibility to severe respiratory viral infections and its therapeutic implications: a narrative review
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Massimiliano Galdiero, Giuditta Benincasa, Ettore Crimi, Neisaliz Figueroa-Marrero, Claudio Napoli, Crimi, E., Benincasa, G., Figueroa-Marrero, N., Galdiero, M., and Napoli, C.
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influenza viru ,Pneumonia, Viral ,coronavirus ,severe acute respiratory syndrome ,medicine.disease_cause ,Article ,influenza virus ,Virus ,Epigenesis, Genetic ,Betacoronavirus ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,030202 anesthesiology ,Intensive care ,Influenza, Human ,medicine ,Humans ,Genetic Predisposition to Disease ,Epigenetics ,Pandemics ,Respiratory Tract Infections ,epigenetic drug ,intensive care ,Coronavirus ,epigenetics ,SARS-CoV-2 ,business.industry ,COVID-19 ,epigenetic drugs ,host–viral interactions ,Acquired immune system ,Chromatin ,coronaviru ,Anesthesiology and Pain Medicine ,chemistry ,DNA methylation ,Immunology ,host–viral interaction ,Coronavirus Infections ,business ,epigenetic - Abstract
Summary The emergence of highly pathogenic strains of influenza virus and coronavirus (CoV) has been responsible for large epidemic and pandemic outbreaks characterised by severe pulmonary illness associated with high morbidity and mortality. One major challenge for critical care is to stratify and minimise the risk of multi-organ failure during the stay in the intensive care unit (ICU). Epigenetic-sensitive mechanisms, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) methylation, histone modifications, and non-coding RNAs may lead to perturbations of the host immune-related transcriptional programmes by regulating chromatin structure and gene expression patterns. Viruses causing severe pulmonary illness can use epigenetic-regulated mechanisms during host–pathogen interaction to interfere with innate and adaptive immunity, adequacy of inflammatory response, and overall outcome of viral infections. For example, Middle East respiratory syndrome-CoV and H5N1 can affect host antigen presentation through DNA methylation and histone modifications. The same mechanisms would presumably occur in patients with coronavirus disease 2019, in which tocilizumab may epigenetically reduce microvascular damage. Targeting epigenetic pathways by immune modulators (e.g. tocilizumab) or repurposed drugs (e.g. statins) may provide novel therapeutic opportunities to control viral–host interaction during critical illness. In this article, we provide an update on epigenetic-sensitive mechanisms and repurposed drugs interfering with epigenetic pathways which may be clinically suitable for risk stratification and beneficial for treatment of patients affected by severe viral respiratory infections.
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- 2020
9. MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19
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Varta Babalyan, Nandini Nair, Daniel D. Bikle, Martin Hewison, Accili Domenico, Marise Lazaretti-Castro, Nicola Napoli, Nicholas Hutchings, Donald W. Landry, Neil Binkley, Anna Maria Formenti, Mahesh V. Madhavan, Aakriti Gupta, Andrea Giustina, John P. Bilezikian, Bilezikian, J. P., Bikle, D., Hewison, M., Lazaretti-Castro, M., Formenti, A. M., Gupta, A., Madhavan, M. V., Nair, N., Babalyan, V., Hutchings, N., Napoli, N., Accili, D., Binkley, N., Landry, D. W., and Giustina, A.
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Vitamin ,medicine.medical_specialty ,T-Lymphocytes ,Endocrinology, Diabetes and Metabolism ,Pneumonia, Viral ,030209 endocrinology & metabolism ,Disease ,Adaptive Immunity ,T-Lymphocytes, Regulatory ,Defensins ,Betacoronavirus ,03 medical and health sciences ,chemistry.chemical_compound ,Th2 Cells ,0302 clinical medicine ,Endocrinology ,Cathelicidins ,Immunity ,Internal medicine ,Autophagy ,medicine ,Vitamin D and neurology ,Humans ,Vitamin D ,Lung ,Pandemics ,SARS-CoV-2 ,business.industry ,COVID-19 ,General Medicine ,Th1 Cells ,medicine.disease ,Acquired immune system ,Immunity, Innate ,Cytokine release syndrome ,chemistry ,030220 oncology & carcinogenesis ,Th17 Cells ,Immunocompetence ,Coronavirus Infections ,Cytokine Release Syndrome ,business ,Cytokine storm ,Antimicrobial Cationic Peptides - Abstract
The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.
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- 2020
10. DNA Methylation Profile of the SREBF2 Gene in Human Fetal Aortas
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Maria D'Armiento, Monica Franzese, Francesco Paolo D'Armiento, Concetta Schiano, Andrea Soricelli, Vincenzo Grimaldi, Rossana Castaldo, Claudio Napoli, Fulvio Zullo, Filomena de Nigris, and Gabriele Saccone
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Pregnancy ,Fetus ,Physiology ,business.industry ,Offspring ,Cholesterol ,medicine.disease ,chemistry.chemical_compound ,chemistry ,CpG site ,medicine ,Epigenetics ,Risk factor ,Cardiology and Cardiovascular Medicine ,business ,Dyslipidemia - Abstract
Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p value SREBF2 gene shows 4 significant differentially hypermethylated sites in the 5′UTR-CpG island. This finding indicates that more effective long-term primary cardiovascular prevention programs need to be designed for the offspring of mothers with hypercholesterolemia. Further studies should be conducted to clarify the epigenetic mechanisms underlying the association between early atherogenesis and maternal hypercholesterolemia during pregnancy.
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- 2021
11. ANMCO POSITION PAPER: on administration of type 2 sodium-glucose co-transporter inhibitors to prevent heart failure in diabetic patients and to treat heart failure patients with and without diabetes
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Edoardo Gronda, Massimo Iacoviello, Claudio Napoli, Pasquale Caldarola, Domenico Gabrielli, Furio Colivicchi, Stefano Urbinati, and Edoardo Mannucci
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Sodium-glucose co-transporter 2 inhibitors ,medicine.medical_specialty ,Heart failure ,chemistry.chemical_compound ,Diabetes mellitus ,Internal medicine ,Type 2 diabetes mellitus ,medicine ,Empagliflozin ,AcademicSubjects/MED00200 ,Dapagliflozin ,Canagliflozin ,Ejection fraction ,business.industry ,Type 2 Diabetes Mellitus ,Articles ,medicine.disease ,chemistry ,Cardiovascular death ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Renal function ,medicine.drug ,Kidney disease - Abstract
This ANMCO (Associazione Nazionale Medici Cardiologi Ospedalieri) position paper aims to analyse the complex action of sodium-glucose co-transporter 2 inhibitors at the level of the kidney and cardiovascular system, focusing on the effect that these molecules have shown in the prevention and treatment of heart failure in diabetic and non-diabetic subjects. The goal was pursued by comparing the data generated with pathophysiology studies and with multicentre controlled studies in large populations. In accordance with the analysis carried out in the document, the following recommendations are issued: (i) canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin are molecules recommended for the prevention of heart failure hospitalizations in type 2 diabetic subjects; (ii) canagliflozin and dapagliflozin are recommended for the prevention of heart failure hospitalizations in type 2 diabetic subjects with severe chronic kidney disease, dapagliflozin proved to be safe and effective also in diabetic subjects; and (iii) dapagliflozin and empagliflozin are recommended to reduce the combined risk of heart failure and cardiovascular death in diabetic and non-diabetic subjects with heart failure and reduced ejection fraction.
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- 2021
12. Immunoglobulins G modulate endothelial function and affect insulin sensitivity in humans
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Raffaele Napoli, Antonio Ruvolo, Fabio Magliulo, Cecilia Nigro, Claudia Miele, Giuseppe Spadaro, Antonio Pecoraro, Antonio Cittadini, Giovanni Esposito, Paola Triggianese, Simona Grassi, Gabriele G. Schiattarella, Amato de Paulis, Nella Prevete, Napoli, R., Ruvolo, A., Triggianese, P., Prevete, N., Schiattarella, G. G., Nigro, C., Miele, C., Magliulo, F., Grassi, S., Pecoraro, A., Cittadini, A., Esposito, G., de Paulis, A., and Spadaro, G.
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Blood Glucose ,Male ,Time Factors ,Brachial Artery ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Medicine (miscellaneous) ,chemistry.chemical_compound ,Insulin ,Medicine ,Infusions, Intravenou ,Brachial artery ,Endothelial dysfunction ,Infusions, Intravenous ,Cells, Cultured ,Nutrition and Dietetics ,biology ,Flow mediated dilation ,Immunoglobulins, Intravenous ,Vasodilation ,Treatment Outcome ,Atherosclerosi ,Female ,Antibody ,Case-Control Studie ,Cardiology and Cardiovascular Medicine ,Human ,medicine.medical_specialty ,Time Factor ,Adolescent ,Nitric Oxide ,Nitric oxide ,Young Adult ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,medicine.artery ,Immunoglobulin ,Humans ,business.industry ,Common variable immunodeficiency ,Endothelial function ,Biomarker ,medicine.disease ,Common Variable Immunodeficiency ,Endocrinology ,chemistry ,Immunoglobulins, Intravenou ,Case-Control Studies ,Immunoglobulin G ,biology.protein ,Endothelium, Vascular ,Insulin Resistance ,business ,Biomarkers - Abstract
Background and aims: Data from animals suggest that immunoglobulins G (IgG) play a mechanistic role in atherosclerosis and diabetes through endothelial dysfunction and insulin resistance. Patients with common variable immunodeficiency (CVID), who have low circulating levels of IgG and are treated with intravenous polyclonal IgG (IVIgG), may provide an ideal model to clarify whether circulating IgG modulate endothelial function and affect insulin sensitivity in humans. Methods and results: We studied 24 patients with CVID and 17 matched healthy controls (HC). Endothelial function was evaluated as flow mediated dilation (FMD) of the brachial artery at baseline and 1, 7, 14, and 21 days after IVIgG infusion in the CVID patients. We measured also plasma glucose, insulin, and calculated the HOMA-IR index. We also investigated the role of human IgG on the production of Nitric Oxide (NO) in vitro in Human Coronary Artery Endothelial Cells (HCAEC). Compared to HC, FMD of CVID patients was significantly impaired at baseline (9.4 ± 0.9 and 7.6 ± 0.6% respectively, p < 0.05) but rose above normal levels 1 and 7 days after IVIgG infusion to return at baseline at 14 and 21 days. Serum insulin concentration and HOMA-IR index dropped by 50% in CVID patients after IVIgG (p < 0.002 vs. baseline). In vitro IgG stimulated NO production in HCAEC. Conclusions: Reduced IgG levels are associated with endothelial dysfunction and IVIgG stimulates endothelial function directly while improving insulin sensitivity. The current findings may suggest an anti-atherogenic role of human IgG.
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- 2020
13. Water perturbed by cellophane: comparison of its physicochemical properties with those of water perturbed with cotton wool or Nafion
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Tamar A. Yinnon, Rosario Oliva, Maria Toscanesi, E. Napoli, Marco Trifuoggi, Roberto Germano, Vittorio Elia, Marcella Niccoli, Valentina Roviello, Angela Amoresano, Antonio Fabozzi, Elia, V., Napoli, E., Germano, R., Roviello, V., Oliva, R., Niccoli, M., Amoresano, A., Toscanesi, M., Trifuoggi, M., Fabozzi, A., and Yinnon, T. A.
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Cellophane ,Mirror symmetry ,Nafion ,02 engineering and technology ,Water insoluble ,01 natural sciences ,law.invention ,chemistry.chemical_compound ,Hydrophilic polymers ,law ,Interfacial water ,Physical and Theoretical Chemistry ,Cellulose ,chemistry.chemical_classification ,Chemistry ,Water ,Polymer ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,010406 physical chemistry ,0104 chemical sciences ,Chemical engineering ,COTTON WOOL ,0210 nano-technology - Abstract
We present experimental data on water repetitively brought in contact with cellophane. Although this hydrophilic polymer is insoluble in water, repetitively immersing it in water changes the liquid’s properties. We compare the physicochemical properties of the water left over after removing the cellophane to those of previously published data on water repetitively brought in contact with other in water insoluble polymers (cotton wool or Nafion). Some of the properties are similar. All the properties considerably differ from those of the Milli-Q® water used. On lyophilizing these waters, solid residues remain. The residues are soluble in water. The chemical nature of the residues differs from that of the perturbing polymers.
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- 2020
14. An insight on type I collagen from horse tendon for the manufacture of implantable devices
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Mohammed Hasan, Maria Lucia Natali, Lorena Campa, Marta Madaghiele, Nunzia Gallo, Loredana Capobianco, Luca Salvatore, Alessandro Sannino, Paola Lunetti, Ludovico Valli, Gabriele Giancane, Anna Napoli, Laura Blasi, Donatella Aiello, Victor V. Borovkov, Amilcare Barca, Simona Bettini, Salvatore, L., Gallo, N., Aiello, D., Lunetti, P., Barca, A., Blasi, L., Madaghiele, M., Bettini, S., Giancane, G., Hasan, M., Borovkov, V., Natali, M. L., Campa, L., Valli, L., Capobianco, L., Napoli, A., and Sannino, A.
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EQUINE COLLAGEN ,Biocompatible Materials ,02 engineering and technology ,Biochemistry ,Collagen Type I ,Tendons ,Mice ,03 medical and health sciences ,Tissue engineering ,Structural Biology ,medicine ,Animals ,Horses ,Type I collagen ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Tissue Engineering ,Tissue Scaffolds ,Equine ,Chemistry ,Horse ,Biomaterial ,General Medicine ,021001 nanoscience & nanotechnology ,Tendon ,medicine.anatomical_structure ,NIH 3T3 Cells ,Immune reaction ,0210 nano-technology ,Biomedical engineering - Abstract
Type I collagen is the most abundant protein of the human body. Due to its favourable properties, collagen extracted from animal tissues is adopted to manufacture a wide range of devices for biomedical applications. Compared to bovine and porcine collagens, which are the most largely used, equine collagen is free from the risk of zoonosis, has no reported immune reactions, and has not religious constraints. In this work, a recently available type I collagen extracted from horse tendon was evaluated and compared with a commercially available collagen isoform derived from the same species and tissue. Detailed physical, chemical and biological investigations were performed, in agreement with the requirements of the current standard for the characterization of type I collagen to be used for the manufacture of Tissue Engineering Medical Products. To the best of our knowledge, this is the first report on the complete primary structure of the investigated collagen.
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- 2020
15. Cloning, Purification, and Characterization of the Catalytic C-Terminal Domain of the Human 3-Hydroxy-3-methyl glutaryl-CoA Reductase: An Effective, Fast, and Easy Method for Testing Hypocholesterolemic Compounds
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Loredana Capobianco, Luigina Muto, Anna Napoli, Rosita Curcio, Carlo Siciliano, Giuseppe Fiermonte, Anna Rita Cappello, Vincenza Dolce, Emanuela Martello, Donatella Aiello, Angelo Vozza, Curcio, R., Aiello, D., Vozza, A., Muto, L., Martello, E., Cappello, A. R., Capobianco, L., Fiermonte, G., Siciliano C., A, Napoli, A., and Dolce, V.
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0106 biological sciences ,Lysis ,Drug Evaluation, Preclinical ,Gene Expression ,Bioengineering ,Reductase ,Affinity chromatography, Bacterial expression, Enzymatic activity, HMGR, MALDI MS and MS/MS, Screening of statin-like molecules ,medicine.disease_cause ,01 natural sciences ,Applied Microbiology and Biotechnology ,Biochemistry ,Chromatography, Affinity ,law.invention ,03 medical and health sciences ,Affinity chromatography ,Tandem Mass Spectrometry ,law ,Catalytic Domain ,010608 biotechnology ,Escherichia coli ,medicine ,Humans ,Amino Acid Sequence ,Cloning, Molecular ,Molecular Biology ,Enzyme Assays ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Chemistry ,C-terminus ,Recombinant Proteins ,Enzyme ,Recombinant DNA ,Hydroxymethylglutaryl CoA Reductases ,Specific activity ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Biotechnology - Abstract
3-hydroxy-3-methyl glutaryl-CoA reductase, also known as HMGR, plays a crucial role in regulating cholesterol biosynthesis and represents the main pharmacological target of statins. In mammals, this enzyme localizes to the endoplasmic reticulum membrane. HMGR includes different regions, an integral N-terminal domain connected by a linker-region to a cytosolic C-terminal domain, the latter being responsible for enzymatic activity. The aim of this work was to design a simple strategy for cloning, expression, and purification of the catalytic C-terminal domain of the human HMGR (cf-HMGR), in order to spectrophotometrically test its enzymatic activity. The recombinant cf-HMGR protein was heterologously expressed in Escherichia coli, purified by Ni+-agarose affinity chromatography and reconstituted in its active form. MALDI mass spectrometry was adopted to monitor purification procedure as a technique orthogonal to the classical Western blot analysis. Protein identity was validated by MS and MS/MS analysis, confirming about 82% of the recombinant sequence. The specific activity of the purified and dialyzed cf-HMGR preparation was enriched about 85-fold with respect to the supernatant obtained from cell lysate. The effective, cheap, and easy method here described could be useful for screening statin-like molecules, so simplifying the search for new drugs with hypocholesterolemic effects.
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- 2019
16. Dynamics of the water quality parameters in the super-intensive culture of Litopenaeus vannamei in BFT system on artificial brackish water
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Luanna do Carmo Neves, Marco Yuri Rodrigues Napoli, Anna Carolina Ferreira Spelta, Kleber Campos Miranda-Filho, João Paulo Silva Lorenzini, Cintia Labussière Nakayama, Gustavo Moreira Alves, Rebeca Valentim Marques, Ângela Maria Quintão Lana, and L.S. Rodrigues
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0106 biological sciences ,Biochemical oxygen demand ,Suspended solids ,Brackish water ,Chemistry ,010604 marine biology & hydrobiology ,Chemical oxygen demand ,04 agricultural and veterinary sciences ,Aquatic Science ,Total dissolved solids ,01 natural sciences ,Salinity ,Animal science ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,Water quality ,Agronomy and Crop Science ,Oxygen saturation - Abstract
The study aimed to characterize the dynamics involved in the water quality parameters in a biofloc system (BFT) during the super-intensive cultivation of Litopenaeus vannamei using two levels of artificial brackish water. The test was designed with two salinity levels, T16 (16‰) and T8 (8‰), with 4 replicates, and 250 shrimps/m2 by 60 days, water analysis and animal performance were studied in each treatment. No significant differences were observed between the two salinities for biochemical oxygen demand (BOD5), total chemical oxygen demand (CODt), and fixed suspended solids (FSS). Using CODt/BOD5, it was possible to identify the water biodegradability and manage the concentration of organic and inorganic matter in the medium. Filtered chemical oxygen demand (CODf) was used to monitor the dissolved organic matter, which was higher in T16. Carbohydrate (molasses) did not control total ammonia reaching in T8 = 1.16±0.64 mg/L. This organic matter addition reduced the growth of chemoautotrophic nitrifying bacteria and interfered in the nitrogen dynamics. Regarding total solids and suspended solids, there was a significant difference between treatments, except for FSS. Dissolved oxygen (DO) and oxygen saturation (sO2) were significantly different between the treatments. The maintenance of a more neutral pH and greater alkalinity were observed, with significant differences between the treatments throughout the whole cultivation. Regarding the shrimp growth performance, the high salinity presented more weight gain, specific growth rate, feed conversion and final biomass, and lower mortality then lower salinity. These results showed that shrimps presented a higher performance in salinity 16‰.
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- 2021
17. ROR1 targeting with the antibody-drug conjugate VLS-101 is effective in Richter syndrome patient–derived xenograft mouse models
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Andrea Iannello, Amy Chadburn, John N. Allan, Nicoletta Vitale, Langdon L. Miller, Tiziana Vaisitti, Arianna Di Napoli, Silvia Deaglio, Esteban Braggio, Mira Ko, Thanh-Trang Lee, Brian J. Lannutti, Francesca Arruga, Katti Jessen, and Richard R. Furman
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Antibody-drug conjugate ,Immunoconjugates ,medicine.drug_class ,Chronic lymphocytic leukemia ,Immunology ,Mice, SCID ,Receptor Tyrosine Kinase-like Orphan Receptors ,Monoclonal antibody ,Biochemistry ,Epitope ,antibody-drug conjugate ,Mice ,chemistry.chemical_compound ,Antineoplastic Agents, Immunological ,Drug Delivery Systems ,Mice, Inbred NOD ,medicine ,Animals ,Humans ,Aminobenzoates ,richter syndrome ,receptor tyrosine kinase-like orphan receptor 1 ,vls-101 ,Mice, Knockout ,Orphan receptor ,Lymphoid Neoplasia ,biology ,business.industry ,Cell Biology ,Hematology ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Xenograft Model Antitumor Assays ,Neoplasm Proteins ,Monomethyl auristatin E ,chemistry ,antibody-drug conjugate, vls-101 ,uc-961 ,ROR1 ,Cancer research ,biology.protein ,Lymphoma, Large B-Cell, Diffuse ,Antibody ,business ,Oligopeptides - Abstract
Richter syndrome (RS) represents the transformation of chronic lymphocytic leukemia (CLL), typically to an aggressive lymphoma. Treatment options for RS are limited and the disease is often fatal. Receptor tyrosine kinase–like orphan receptor 1 (ROR1) is expressed on CLL cells and other cancers but not on healthy adult tissues, making it an attractive, tumor-specific therapeutic target. VLS-101 is being developed as an antibody-drug conjugate (ADC) for therapy of ROR1-expressing (ROR1+) cancers. VLS-101 comprises UC-961 (a humanized immunoglobulin G1 monoclonal antibody that binds an extracellular epitope of human ROR1), a maleimidocaproyl-valine-citrulline-para-aminobenzoate linker, and the antimicrotubule cytotoxin monomethyl auristatin E (MMAE). VLS-101 binding to ROR1 results in rapid cellular internalization and delivery of MMAE to induce tumor cell death. We studied 4 RS patient-derived xenografts (RS-PDXs) with varying levels of ROR1 expression (11%, 32%, 85%, and 99% of cells). VLS-101 showed no efficacy in the lowest-expressing RS-PDX but induced complete remissions in those with higher levels of ROR1 expression. Responses were maintained during the posttherapy period, particularly after higher VLS-101 doses. In systemic ROR1+ RS-PDXs, VLS-101 dramatically decreased tumor burden in all RS-colonized tissues and significantly prolonged survival. Animals showed no adverse effects or weight loss. Our results confirm ROR1 as a target in RS and demonstrate the therapeutic potential of using an ADC directed toward ROR1 for the treatment of hematological cancers. A phase 1 clinical trial of VLS-101 (NCT03833180) is ongoing in patients with RS and other hematological malignancies.
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- 2021
18. Habitual coffee and caffeinated beverages consumption is inversely associated with arterial stiffness and central and peripheral blood pressure
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Sofia Gabutti, Chiara Troiani, Stefano Scanzio, Emiliano De Napoli, Rosaria Del Giorno, Kevyn Stefanelli, and Luca Gabutti
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0301 basic medicine ,medicine.medical_specialty ,Diastole ,Blood Pressure ,030209 endocrinology & metabolism ,Pulse Wave Analysis ,Coffee ,03 medical and health sciences ,chemistry.chemical_compound ,Vascular Stiffness ,0302 clinical medicine ,Internal medicine ,medicine ,Prospective cohort study ,Pulse wave velocity ,030109 nutrition & dietetics ,business.industry ,Blood Pressure Monitoring, Ambulatory ,medicine.disease ,Peripheral blood ,Peripheral ,chemistry ,Cardiology ,Arterial stiffness ,Aortic stiffness ,business ,Caffeine ,Food Science - Abstract
The effects of chronic coffee consumption on the cardiovascular system are still under debate. Aortic stiffness, wave reflections, and central and peripheral blood pressure (BP) are milestone indicators of cardiovascular-risk. We sought to investigate the association between coffee and caffeine consumption, arterial stiffness, and central/peripheral BP. Aortic stiffness was evaluated via pulse wave velocity (PWV); wave reflections with the augmentation index (AIx);peripheral systolic BP (SBP), diastolic BP (DBP), and central BP (cSBP/cDBP) were non-invasively assessed. Coffee and caffeine consumption was ascertained using a questionnaire. A linear inverse relationship between coffee and caffeine consumption and arterial stiffness and central and peripheral BP was found.Light coffee and caffeine consumers showed β-coefficients for PWV-0.15, SBP-3.61, DBP-2.48, cSBP-3.21, and cDBP-2.18 (all p values < 0.05).Present findings suggest that coffee and caffeine consumption is inversely associated with arterial stiffness and central and peripheral BP in a large population sample. Interventional prospective studies are needed to demonstrate the causal association.
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- 2021
19. Chemical composition, safety and efficacy of Pistacia vera L. oleoresin essential oils in experimental wounds
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Amel Boudjelal, Edoardo Napoli, Davide Gentile, Giuseppe Ruberto, Sarra Chabane, and Abderrahim Benkhaled
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integumentary system ,Pistacia ,biology ,Traditional medicine ,Chemistry ,toxicity ,a-pinene ,wound healing activity ,General Chemistry ,Pistacia vera L ,biology.organism_classification ,essential oil ,law.invention ,chemistry.chemical_compound ,law ,hemic and lymphatic diseases ,Oleoresin ,Chemical composition ,Essential oil - Abstract
The aims of the study were to evaluate the wound-healing properties in an in-vivo model of the essential oils from Algerian and Italian Pistacia vera L. oleoresins. The essential oils (EOs) were obtained by hydrodistillation of oleoresins from the trunk of plants. They were analyzed by GC-FID and GC-MS, ?-pinene was the main constituent of both EOs. The wound-healing potential of P. vera EOs was investigated using an excision wound model in rabbits. The EOs were mixed with petroleum jelly to obtain a topical ointment with a final concentration of 5%. The percentage of the evolution of wound contraction was calculated and histological sections of tissues were examined. Both preparations possess wound-healing activities comparable to that of the reference drug Cicatryl-Bio. Some EOs exhibit a wound-healing potential suggesting that they could find a place in modern therapy.
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- 2021
20. MALDI Mass Spectrometry Study of Glycated Substrates
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Anna Napoli
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Chromatography ,Mechanics of Materials ,Chemistry ,Mechanical Engineering ,010401 analytical chemistry ,General Materials Science ,02 engineering and technology ,021001 nanoscience & nanotechnology ,0210 nano-technology ,Mass spectrometry ,01 natural sciences ,0104 chemical sciences - Abstract
In this report, we proposed a MALDI mass spectrometry-based approach to study the formation of glycated species by coupling carbonyl aldehydes of sugar and molecules nucleophilic groups via enzymatic oxidation. The proposed enzymatic glycation in vitro could be a simple method to obtain well-defined substrates useful to study biological properties and activities of proteins in clinical samples, during oxidative stress and disease.
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- 2021
21. Content variability of bioactive secondary metabolites in Hypericum perforatum L
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Antonio Giovino, Silvia Lazzara, Edoardo Napoli, Giuseppe Ruberto, Alessandra Carrubba, Carrubba A., Lazzara S., Giovino A., Ruberto G., and Napoli E.
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Adhyperforin ,St. john worth ,biology ,Traditional medicine ,phytochemical variability ,secondary metabolites ,Hypericum perforatum ,Plant Science ,Hypericaceae ,biology.organism_classification ,Biochemistry ,Hypericin ,chemistry.chemical_compound ,Hyperforin ,cultivation ,chemistry ,Phytochemical ,Polyphenol ,Cultivation, Hypericum perforatum, Phytochemical variability, Secondary metabolites, St John's Wort ,Hypericum ,Agronomy and Crop Science ,Biotechnology - Abstract
St John’s Wort (Hypericum perforatum L.; Hypericaceae) is a perennial medicinal herb widespread and largely used in folk medicine inside the Mediterranean basin. Many bioactive compounds have been identified within its extracts. Under a pharmacological point of view, the most important of them belong to the chemical classes of naphthodianthrones, phloroglucinols and polyphenols. Many factors have been claimed responsible for the phytochemical variability in Hypericum perforatum, such as genotype, geographical origin, harvesting stage and age of the plants. Yet, when harvested plant material is addressed to the industry, the standardization of the active ingredients over cultivation years is a crucial issue. With the aim to detect the stability over years and genotypes of several bioactive Hypericum compounds, seven Hypericum biotypes retrieved from different Italian geographical areas were cultivated in 2015 and 2016, and their aerial flowering parts were analyzed. Naphthodianthrones (hypericin and its biosynthetic precursors), phloroglucinols (hyperforin and adhyperforin), and main polyphenols were determined by HPLC-DAD analysis. The results were statistically evaluated through ANOVA, and the stability over cultivation years of the tested genotypes was assessed. In rather all the examined metabolites, the ANOVA revealed a remarkable effect of both factors “year” (Y) and “provenance” (P), but the occurrence of significant “Y x P” interactions evidenced that the effect of climatic variability was often different according to the genotype. The evaluation of the stability level between years evidenced that only one biotype out of seven exhibited constantly higher-than-average amounts of rather all identified metabolites.
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- 2021
22. Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype
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Marco Coazzoli, Claudia Moscheni, Cecilia Prata, Clara De Palma, Emilio Clementi, Pasquale Marrazzo, Ilaria Di Renzo, Cristiana Perrotta, Marco Malaguti, Alessandra Napoli, Silvia Zecchini, Matteo Giovarelli, Silvana Hrelia, Maria Cristina Barbalace, Elisabetta Catalani, Paulina Roux-Biejat, Maria Teresa Bassi, Davide Cervia, and Roux-Biejat P, Coazzoli M, Marrazzo P, Zecchini S, Di Renzo I, Prata C, Napoli A, Moscheni C, Giovarelli M, Barbalace MC, Catalani E, Bassi MT, De Palma C, Cervia D, Malaguti M, Hrelia S, Clementi E, Perrotta C.
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Satellite Cells, Skeletal Muscle ,QH301-705.5 ,macrophage phenotype ,Inflammation ,Article ,Cardiotoxin ,Immune system ,medicine ,Animals ,Regeneration ,Macrophage ,Biology (General) ,acid sphingomyelinase ,Muscle, Skeletal ,Cell Proliferation ,Mice, Knockout ,muscle regeneration ,Myogenesis ,Chemistry ,Macrophages ,Regeneration (biology) ,Cell Polarity ,Skeletal muscle ,Cell Differentiation ,General Medicine ,Cell biology ,Enzyme Activation ,Phenotype ,Sphingomyelin Phosphodiesterase ,medicine.anatomical_structure ,inflammation ,Acid sphingomyelinase ,medicine.symptom ,Signal Transduction ,medicine.drug - Abstract
Skeletal muscle regeneration is a complex process involving crosstalk between immune cells and myogenic precursor cells, i.e., satellite cells. In this scenario, macrophage recruitment in damaged muscles is a mandatory step for tissue repair since pro-inflammatory M1 macrophages promote the activation of satellite cells, stimulating their proliferation and then, after switching into anti-inflammatory M2 macrophages, they prompt satellite cells’ differentiation into myotubes and resolve inflammation. Here, we show that acid sphingomyelinase (ASMase), a key enzyme in sphingolipid metabolism, is activated after skeletal muscle injury induced in vivo by the injection of cardiotoxin. ASMase ablation shortens the early phases of skeletal muscle regeneration without affecting satellite cell behavior. Of interest, ASMase regulates the balance between M1 and M2 macrophages in the injured muscles so that the absence of the enzyme reduces inflammation. The analysis of macrophage populations indicates that these events depend on the altered polarization of M1 macrophages towards an M2 phenotype. Our results unravel a novel role of ASMase in regulating immune response during muscle regeneration/repair and suggest ASMase as a supplemental therapeutic target in conditions of redundant inflammation that impairs muscle recovery.
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- 2021
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23. Underdiagnosis and undertreatment of osteoporotic patients admitted in internal medicine wards in Italy between 2010 and 2016 (the REPOSI Register)
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Pepe J., Agosti P., Cipriani C., Tettamanti M., Nobili A., Colangelo L., Santori R., Cilli M., Minisola S., Mannucci P. M., Pietrangelo A., Perticone F., Violi F., Corazza G. R., Corrao S., Marengoni A., Salerno F., Cesari M., Pasina L., Cortesi C. F. L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Mattioli I., Biolo G., Zanetti M., Bartelloni G., Vanoli M., Grignani G., Pulixi E. A., Lupattelli G., Bianconi V., Alcidi R., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Beneduce V., Cacioppo F., Natoli G., Mularo S., Raspanti M., Zoli M., Matacena M. L., Orio G., Magnolfi E., Serafini G., Simili A., Palasciano G., Modeo M. E., Di Gennaro C., Cappellini M. D., Fabio G., De Amicis M. M., De Luca G., Scaramellini N., Rossi P. D., Damanti S., Clerici M., Leoni S., Di Mauro A. D., Di Sabatino A., Miceli E., Lenti M. V., Pisati M., Dominioni C. C., Pontremoli R., Beccati V., Nobili G., Leoncini G., Anastasio L., Carbone M., Cipollone F., Guagnano M. T., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Giorgi A., Gracin C., Zuccala G., D'Aurizio G., Romanelli G., Volpini A., Lucente D., Picardi A., Gentilucci U. V., Gallo P., Bellelli G., Corsi M., Antonucci C., Sidoli C., Principato G., Arturi F., Succurro E., Tassone B., Giofre F., Serra M. G., Bleve M. A., Brucato A., De Falco T., Fabris F., Bertozzi I., Bogoni G., Rabuini M. V., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., Paolisso G., Rizzo M. R., Catalano C., Borghi C., Strocchi E., Ianniello E., Soldati M., Schiavone S., Bragagni A., Sabba C., Vella F. S., Suppressa P., De Vincenzo G. M., Comitangelo A., Amoruso E., Custodero C., Fenoglio L., Falcetta A., Fracanzani A. L., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Colombo G., Monzani V., Savojardo V., Ceriani G., Pallini G., Montecucco F., Ottonello L., Caserza L., Vischi G., Liberato N. L., Tognin T., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Pisciotta M. S., Bellucci F. B., Buffelli S., Montrucchio G., Peasso P., Favale E., Poletto C., Margaria C., Sanino M., Perri L., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Diprizio R. D., Bertolotti M., Mussi C., Lancellotti G., Libbra M. V., Galassi M., Grassi Y., Greco A., Sciacqua A., Perticone M., Battaglia R., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Mattioli M., Martino G. P., Biondi L., Pettinari P., Ghio R., Col A. D., Labbadia G., Afeltra A., Marigliano B., Pipita M. E., Castellino P., Zanoli L., Gennaro A., Gaudio A., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Vigorito C., Cittadini A., Moreo G., Prolo S., Pina G., Ballestrero A., Ferrando F., Gonella R., Cerminara D., Berra S., Dassi S., Nava M. C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Sechi L., Catena C., Colussi G., Cavarape A., Da Porto A., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G. P., Maggio M. G., Morganti S., Artoni A., Grossi M., Del Giacco S., Firinu D., Costanzo G., Argiolas G., Montalto G., Licata A., Montalto F. A., Corica F., Basile G., Catalano A., Bellone F., Principato C., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Imperiale G. N., Pirisi M., Fra G. P., Sola D., Bellan M., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Napoli F., Aiello I., Landolfi R., Montalto M., Mirijello A., Ghidoni S., Salvatore T., Monaco L., Ricozzi C., Pilotto A., Indiano I., Gandolfo F., Pepe, Jessica, Agosti, Pasquale, Cipriani, Cristiana, Tettamanti, Mauro, Nobili, Alessandro, Colangelo, Luciano, Santori, Rachele, Cilli, Mirella, Minisola, Salvatore, Rinaldi, Luca, Pepe J, Agosti P, Cipriani C, Tettamanti M, Nobili A, Colangelo L, Santori R, Cilli M, Minisola S, Borghi C., Pepe, J., Agosti, P., Cipriani, C., Tettamanti, M., Nobili, A., Colangelo, L., Santori, R., Cilli, M., Minisola, S., Mannucci, P. M., Pietrangelo, A., Perticone, F., Violi, F., Corazza, G. R., Corrao, S., Marengoni, A., Salerno, F., Cesari, M., Pasina, L., Cortesi, C. F. L., Miglio, G., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Mattioli, I., Biolo, G., Zanetti, M., Bartelloni, G., Vanoli, M., Grignani, G., Pulixi, E. A., Lupattelli, G., Bianconi, V., Alcidi, R., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Beneduce, V., Cacioppo, F., Natoli, G., Mularo, S., Raspanti, M., Zoli, M., Matacena, M. L., Orio, G., Magnolfi, E., Serafini, G., Simili, A., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Fabio, G., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Leoni, S., Di Mauro, A. D., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Pontremoli, R., Beccati, V., Nobili, G., Leoncini, G., Anastasio, L., Carbone, M., Cipollone, F., Guagnano, M. T., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Giorgi, A., Gracin, C., Zuccala, G., D'Aurizio, G., Romanelli, G., Volpini, A., Lucente, D., Picardi, A., Gentilucci, U. V., Gallo, P., Bellelli, G., Corsi, M., Antonucci, C., Sidoli, C., Principato, G., Arturi, F., Succurro, E., Tassone, B., Giofre, F., Serra, M. G., Bleve, M. A., Brucato, A., De Falco, T., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., Paolisso, G., Rizzo, M. R., Catalano, C., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Schiavone, S., Bragagni, A., Sabba, C., Vella, F. S., Suppressa, P., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Custodero, C., Fenoglio, L., Falcetta, A., Fracanzani, A. L., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Colombo, G., Monzani, V., Savojardo, V., Ceriani, G., Pallini, G., Montecucco, F., Ottonello, L., Caserza, L., Vischi, G., Liberato, N. L., Tognin, T., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Pisciotta, M. S., Bellucci, F. B., Buffelli, S., Montrucchio, G., Peasso, P., Favale, E., Poletto, C., Margaria, C., Sanino, M., Perri, L., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Diprizio, R. D., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Galassi, M., Grassi, Y., Greco, A., Sciacqua, A., Perticone, M., Battaglia, R., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Gennaro, A., Gaudio, A., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Vigorito, C., Cittadini, A., Moreo, G., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Gonella, R., Cerminara, D., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Sechi, L., Catena, C., Colussi, G., Cavarape, A., Da Porto, A., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Grossi, M., Del Giacco, S., Firinu, D., Costanzo, G., Argiolas, G., Montalto, G., Licata, A., Montalto, F. A., Corica, F., Basile, G., Catalano, A., Bellone, F., Principato, C., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., La Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Imperiale, G. N., Pirisi, M., Fra, G. P., Sola, D., Bellan, M., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Napoli, F., Aiello, I., Landolfi, R., Montalto, M., Mirijello, A., Ghidoni, S., Salvatore, T., Monaco, L., Ricozzi, C., Pilotto, A., Indiano, I., Gandolfo, F., Pepe J., Agosti P., Cipriani C., Tettamanti M., Nobili A., Colangelo L., Santori R., Cilli M., Minisola S., Mannucci P.M., Pietrangelo A., Perticone F., Violi F., Corazza G.R., Corrao S., Marengoni A., Salerno F., Cesari M., Pasina L., Cortesi C.F.L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Mattioli I., Biolo G., Zanetti M., Bartelloni G., Vanoli M., Grignani G., Pulixi E.A., Lupattelli G., Bianconi V., Alcidi R., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Beneduce V., Cacioppo F., Natoli G., Mularo S., Raspanti M., Zoli M., Matacena M.L., Orio G., Magnolfi E., Serafini G., Simili A., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Fabio G., De Amicis M.M., De Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Leoni S., Di Mauro A.D., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Pontremoli R., Beccati V., Nobili G., Leoncini G., Anastasio L., Carbone M., Cipollone F., Guagnano M.T., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Giorgi A., Gracin C., Zuccala G., D'Aurizio G., Romanelli G., Volpini A., Lucente D., Picardi A., Gentilucci U.V., Gallo P., Bellelli G., Corsi M., Antonucci C., Sidoli C., Principato G., Arturi F., Succurro E., Tassone B., Giofre F., Serra M.G., Bleve M.A., Brucato A., De Falco T., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., Paolisso G., Rizzo M.R., Catalano C., Borghi C., Strocchi E., Ianniello E., Soldati M., Schiavone S., Bragagni A., Sabba C., Vella F.S., Suppressa P., De Vincenzo G.M., Comitangelo A., Amoruso E., Custodero C., Fenoglio L., Falcetta A., Fracanzani A.L., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Colombo G., Monzani V., Savojardo V., Ceriani G., Pallini G., Montecucco F., Ottonello L., Caserza L., Vischi G., Liberato N.L., Tognin T., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Pisciotta M.S., Bellucci F.B., Buffelli S., Montrucchio G., Peasso P., Favale E., Poletto C., Margaria C., Sanino M., Perri L., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Diprizio R.D., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Galassi M., Grassi Y., Greco A., Sciacqua A., Perticone M., Battaglia R., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Col A.D., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Gennaro A., Gaudio A., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Vigorito C., Cittadini A., Moreo G., Prolo S., Pina G., Ballestrero A., Ferrando F., Gonella R., Cerminara D., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Sechi L., Catena C., Colussi G., Cavarape A., Da Porto A., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Grossi M., Del Giacco S., Firinu D., Costanzo G., Argiolas G., Montalto G., Licata A., Montalto F.A., Corica F., Basile G., Catalano A., Bellone F., Principato C., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Imperiale G.N., Pirisi M., Fra G.P., Sola D., Bellan M., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Napoli F., Aiello I., Landolfi R., Montalto M., Mirijello A., Ghidoni S., Salvatore T., Monaco L., Ricozzi C., Pilotto A., Indiano I., Gandolfo F., Pepe, J, Agosti, P, Cipriani, C, Tettamanti, M, Nobili, A, Colangelo, L, Santori, R, Cilli, M, Minisola, S, Mannucci, P, Pietrangelo, A, Perticone, F, Violi, F, Corazza, G, Corrao, S, Marengoni, A, Salerno, F, Cesari, M, Pasina, L, Cortesi, C, Miglio, G, Ardoino, I, Novella, A, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Mattioli, I, Biolo, G, Zanetti, M, Bartelloni, G, Vanoli, M, Grignani, G, Pulixi, E, Lupattelli, G, Bianconi, V, Alcidi, R, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Beneduce, V, Cacioppo, F, Natoli, G, Mularo, S, Raspanti, M, Zoli, M, Matacena, M, Orio, G, Magnolfi, E, Serafini, G, Simili, A, Palasciano, G, Modeo, M, Di Gennaro, C, Cappellini, M, Fabio, G, De Amicis, M, De Luca, G, Scaramellini, N, Rossi, P, Damanti, S, Clerici, M, Leoni, S, Di Mauro, A, Di Sabatino, A, Miceli, E, Lenti, M, Pisati, M, Dominioni, C, Pontremoli, R, Beccati, V, Nobili, G, Leoncini, G, Anastasio, L, Carbone, M, Cipollone, F, Guagnano, M, Rossi, I, Mancuso, G, Calipari, D, Bartone, M, Delitala, G, Berria, M, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Giorgi, A, Gracin, C, Zuccala, G, D'Aurizio, G, Romanelli, G, Volpini, A, Lucente, D, Picardi, A, Gentilucci, U, Gallo, P, Bellelli, G, Corsi, M, Antonucci, C, Sidoli, C, Principato, G, Arturi, F, Succurro, E, Tassone, B, Giofre, F, Serra, M, Bleve, M, Brucato, A, De Falco, T, Fabris, F, Bertozzi, I, Bogoni, G, Rabuini, M, Prandini, T, Manfredini, R, Fabbian, F, Boari, B, De Giorgi, A, Tiseo, R, Paolisso, G, Rizzo, M, Catalano, C, Borghi, C, Strocchi, E, Ianniello, E, Soldati, M, Schiavone, S, Bragagni, A, Sabba, C, Vella, F, Suppressa, P, De Vincenzo, G, Comitangelo, A, Amoruso, E, Custodero, C, Fenoglio, L, Falcetta, A, Fracanzani, A, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Peyvandi, F, Rossio, R, Colombo, G, Monzani, V, Savojardo, V, Ceriani, G, Pallini, G, Montecucco, F, Ottonello, L, Caserza, L, Vischi, G, Liberato, N, Tognin, T, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Pisciotta, M, Bellucci, F, Buffelli, S, Montrucchio, G, Peasso, P, Favale, E, Poletto, C, Margaria, C, Sanino, M, Perri, L, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Diprizio, R, Bertolotti, M, Mussi, C, Lancellotti, G, Libbra, M, Galassi, M, Grassi, Y, Greco, A, Sciacqua, A, Perticone, M, Battaglia, R, Maio, R, Stanghellini, V, Ruggeri, E, del Vecchio, S, Salvi, A, Leonardi, R, Damiani, G, Capeci, W, Mattioli, M, Martino, G, Biondi, L, Pettinari, P, Ghio, R, Col, A, Labbadia, G, Afeltra, A, Marigliano, B, Pipita, M, Castellino, P, Zanoli, L, Gennaro, A, Gaudio, A, Saracco, V, Fogliati, M, Bussolino, C, Mete, F, Gino, M, Vigorito, C, Cittadini, A, Moreo, G, Prolo, S, Pina, G, Ballestrero, A, Ferrando, F, Gonella, R, Cerminara, D, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Gruden, G, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Sechi, L, Catena, C, Colussi, G, Cavarape, A, Da Porto, A, Passariello, N, Rinaldi, L, Berti, F, Famularo, G, Tarsitani, P, Castello, R, Pasino, M, Ceda, G, Maggio, M, Morganti, S, Artoni, A, Grossi, M, Del Giacco, S, Firinu, D, Costanzo, G, Argiolas, G, Montalto, G, Licata, A, Montalto, F, Corica, F, Basile, G, Catalano, A, Bellone, F, Principato, C, Malatino, L, Stancanelli, B, Terranova, V, Di Marca, S, Di Quattro, R, La Malfa, L, Caruso, R, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Ticinesi, A, Nouvenne, A, Minuz, P, Fondrieschi, L, Imperiale, G, Pirisi, M, Fra, G, Sola, D, Bellan, M, Porta, M, Riva, P, Quadri, R, Larovere, E, Novelli, M, Scanzi, G, Mengoli, C, Provini, S, Ricevuti, L, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Napoli, F, Aiello, I, Landolfi, R, Montalto, M, Mirijello, A, Ghidoni, S, Salvatore, T, Monaco, L, Ricozzi, C, Pilotto, A, Indiano, I, and Gandolfo, F
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Osteoporosis ,030209 endocrinology & metabolism ,NO ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Rating scale ,Internal medicine ,Diabetes mellitus ,Vitamin D and neurology ,Internal Medicine ,Medicine ,eractures ,Humans ,Bisphosphonate ,Medical diagnosis ,bisphosphonates ,osteoporosis ,vitamin D ,Vitamin D ,Aged ,Creatinine ,Rehabilitation ,LS7_9 ,Bisphosphonates ,Fractures ,business.industry ,Osteoporosi ,medicine.disease ,Hospitalization ,Fracture ,chemistry ,Italy ,030220 oncology & carcinogenesis ,Geriatric Depression Scale ,business - Abstract
Purpose: To evaluate clinical features, treatments, and outcomes of osteoporotic patients admitted to internal medicine and geriatric wards compared with non-osteoporotic patients (REPOSI registry). Methods: We studied 4714 patients hospitalized between 2010 and 2016. We reported age, sex, educational level, living status, comorbidities and drugs taken, Cumulative Illness Rating Scale (CIRS), Barthel Index, Short-Blessed Test, 4-item Geriatric Depression Scale, serum hemoglobin, creatinine, and clinical outcomes. Osteoporosis was defined based on the diagnoses recorded at admission, according to the following ICD9: 733, 805-813, 820-823. Results: Twelve percent of the patients had a preadmission diagnosis of osteoporosis. Only 20% of these had been prescribed oral bisphosphonates; 34% were taking vitamin D supplements. Osteoporotic patients were significantly older, with lower BMI, higher CIRS, and taking more drugs. They were significantly more depressed, less independent, with a higher severity of cognitive impairment compared with non-osteoporotic patients. At discharge, the number of patients receiving treatment for osteoporosis did not change. Length of stay and inhospital mortality did not differ between groups. Osteoporotic patients were more frequently nonhome discharged compared with those without osteoporosis (14.8 vs. 7.9%, p = 0.0007), mostly discharged to physical therapy or rehabilitation (8.8 vs. 2.5% of patients, p < 0.0001). Among osteoporotic patients deceased 3 months after discharge, the number of those treated with vitamin D, with or without calcium supplements, was significantly lower compared with survivors (12 vs. 32%, p = 0.0168). Conclusions: The diagnosis of osteoporosis is poorly considered both during hospital stay and at discharge; osteoporotic patients are frailer compared to non-osteoporotic patients.
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- 2021
24. Sarcopenia and homocysteine: is there a possible association in the elderly? A narrative review
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Alessandra Vincenti, Hellas Cena, Massimo Negro, Chiara Elena Tomasinelli, Rachele De Giuseppe, and Ilaria Di Napoli
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0301 basic medicine ,Gerontology ,Sarcopenia ,Physical disability ,Homocysteine ,Population ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Humans ,Medicine ,Muscle Strength ,Muscle, Skeletal ,education ,Association (psychology) ,Aged ,education.field_of_study ,030109 nutrition & dietetics ,Nutrition and Dietetics ,business.industry ,Physical Functional Performance ,Micronutrient ,medicine.disease ,B vitamins ,chemistry ,Ageing ,business - Abstract
Background:Sarcopenia (SA) is a progressive skeletal muscle disorder, associated with increased risk of adverse outcomes, including falls, fractures, physical disability and mortality. Several risks factors may contribute to the development of SA in the elderly; among them, nutrition plays a key role in muscle health. The elderly are at risk of inadequate intake in terms of micronutrients affecting muscle homeostasis, such as B vitamins, related to homocysteine (Hcy) metabolism.Objectives and methods:This narrative review analysed the association between increased Hcy levels and SA, according to the criteria of the International Working Group on Sarcopenia, the European Working Group on Sarcopenia in Older People and the Asian Working Group for Sarcopenia. The authors focused not only on SA per se but also on exploring the association between increased Hcy levels and components of SA, including muscle mass, muscle strength and physical performance.Results:Results are inconsistent, except for muscle mass, showing no significant associations with Hcy levels.Conclusions:Few and conflicting data emerged in this review on the association between SA and increased Hcy levels due to numerous differences between studies that change the significance of the association of Hcy and SA, as well as the muscle strength, muscle mass and physical performance. Furthermore, because the ageing process is not uniform in the population owing to differences in genetics, lifestyle and general health, chronological age fails to address the observed heterogeneity among the ‘elderly’ of the studies reported in this revision. Therefore, further studies are still needed.
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- 2021
25. Volatile organic compounds produced by Trichoderma sp. morphophysiologically altered maize growth at initial stages
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João Henrique da Silva Luz, Aloisio Freitas Chagas Junior, Rubens Ribeiro da Silva, Juliana Lopes dos Santos, Rodrigo Silva de Oliveira, Renato de Almeida Sarmento, Hanrara Pires de Oliveira, Evandro Alves Ribeiro, and Bruno Henrique Di Napoli Nunes
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carbohydrates (lipids) ,Horticulture ,Chemistry ,technology, industry, and agriculture ,food and beverages ,macromolecular substances ,Plant Science ,complex mixtures ,Agronomy and Crop Science ,Trichoderma sp - Abstract
Fungi of the genus Trichoderma are important microorganisms for increasing plant growth. However, few studies have evaluated the potential of volatile compounds produced by the fungus Trichoderma spp. and it's potential as promoters and beneficiaries with respect to maize cultivation. Thus, this work aimed to evaluate the efficiency of volatile compounds produced by Trichoderma spp. and their potential for morphophysiological improvement in the initial growth of corn crops. The experiment was conducted in a factorial scheme (2x6+1), arranged in a completely randomized design, with two evaluation times (7 and 15 days after emergence (DAE) and five Trichoderma spp. isolates (plus one control). The isolates were classified as the following species and identified with the following codes: UFT-25: Trichoderma harzianum; UFT-37: Trichoderma pinnatium; UFT-57: Trichoderma virens; UFT-201: Trichoderma asperellum and UFT-204: Trichoderma longibrachiatum. The volatile compounds produced by Trichoderma spp. and inoculated in culture medium present in each experimental unit without direct contact with the roots of the plants, promoted an increase mass production and changed morphology and physiology, especially plant height, leaf area, absolute and relative growth rate, Falker chlorophyll index, instantaneous carboxylation efficiency (RuBisCo), and net photosynthesis rate
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- 2021
26. Choline kinase alpha impairment overcomes TRAIL resistance in ovarian cancer cells
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Delia Mezzanzanica, Francesco Raspagliesi, Giulia Garrone, Mariangela Figini, Alessandra Napoli, Alessandro Satta, Adalberto Cavalleri, Marina Bagnoli, Loris De Cecco, Egidio Iorio, Antonella Tomassetti, and Andrea Rizzo
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0301 basic medicine ,Cancer Research ,Programmed cell death ,Choline kinase ,medicine.medical_treatment ,Choline kinase alpha ,TRAIL ,lcsh:RC254-282 ,TNF-Related Apoptosis-Inducing Ligand ,03 medical and health sciences ,0302 clinical medicine ,Ovarian cancer ,medicine ,Humans ,Cytotoxic T cell ,Ovarian Neoplasms ,Chemistry ,Research ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Cytokine ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Apoptosis resistance ,Cancer research ,Metabolic alterations ,Female ,Tumor necrosis factor alpha ,Ex vivo - Abstract
Background Choline kinase-α (ChoKα/CHKA) overexpression and hyper-activation sustain altered choline metabolism conferring the cholinic phenotype to epithelial ovarian cancer (OC), the most lethal gynecological tumor. We previously proved that CHKA down-modulation reduced OC cell aggressiveness and increased sensitivity to in vitro chemotherapeutics’ treatment also affecting intracellular content of one-carbon metabolites. In tumor types other than ovary, methionine decrease was shown to increase sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-receptor 2 triggering. These effects were suggestive of a potential role for ChoKα in regulating susceptibility to TRAIL cytokine. Methods The relationship between ChoKα/CHKA and TRAIL-receptor 2 (TRAIL-R2) expression was investigated in silico in OC patients’ GEO datasets and in vitro in a panel of OC cell lines upon transient CHKA silencing (siCHKA). The effect of siCHKA on metabolites content was assessed by LC-MS. The triggered apoptotic signalling was studied following soluble-TRAIL or anti-TRAIL-R2 agonist antibody treatment. Lipid rafts were isolated by Triton X-100 fractionation. Preclinical ex vivo studies were performed in OC cells derived from patients’ ascites using autologous PBLs as effectors and a bispecific anti-TRAIL-R2/anti-CD3 antibody as triggering agent. Results Here we demonstrate that siCHKA specifically overcomes resistance to TRAIL-mediated apoptosis in OC cells. Upon siCHKA we detected: a significant sensitization to caspase-dependent apoptosis triggered by both soluble TRAIL and anti-TRAIL-R2 agonist antibody, a specific increase of TRAIL-R2 expression and TRAIL-R2 relocation into lipid rafts. In siCHKA-OC cells the acquired TRAIL sensitivity was completely reverted upon recovery of ChoKα expression but, at variance of other tumor cell types, TRAIL sensitivity was not efficiently phenocopied by methionine deprivation. Of note, we were also able to show that siCHKA sensitized tumor cells derived ex vivo from OC patients’ ascites to the cytotoxic activity of autologous lymphocytes redirected by a bispecific anti-TRAIL-R2/anti-CD3 antibody. Conclusions Our findings suggest that ChoKα/CHKA impairment, by restoring drug-induced or receptor-mediated cell death, could be a suitable therapeutic strategy to be used in combination with chemotherapeutics or immunomodulators to improve OC patients’ outcome.
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- 2021
27. TECHNOLOGICAL EVALUATION OF CUBATI/BRAZIL MONTMORILLONITE / AVALIAÇÃO TECNOLÓGICA DA MONTMORILLONITA DE CUBATI/BRASIL
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Fernanda Arruda Nogueira Gomes da Silva, Carla Napoli Barbato, Filipe de Albuquerque Gomes Brasileiro, Lídia Yokoyama, Bruna de Lemos Novo, and Luiz Carlos Bertolino
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Marketing ,Pharmacology ,Organizational Behavior and Human Resource Management ,Strategy and Management ,Pharmaceutical Science ,chemistry.chemical_compound ,Montmorillonite ,chemistry ,Drug Discovery ,Cation-exchange capacity ,Zeta potential ,Kaolinite ,Surface charge ,Fourier transform infrared spectroscopy ,Calcium oxide ,Sodium carbonate ,Nuclear chemistry - Abstract
The aim of this work was the technological characterization of sample fraction from Cubati region, Pedra Lavrada – Paraiba State, Brazil, in order to evaluate its further applications as drug adsorber and as oil drilling fluid. The sample had been properly processed and characterized by X-ray diffractometry, X-ray fluorescence spectroscopy, cation exchange capacity, thermo-differential and thermogravimetric analysis, determination of textural properties by BET and B.J.H. methods, Fourier transform infrared spectroscopy and surface charge measurements by means of Zeta potential. The results obtained showed that the studied sample is essentially composed by montmorillonite (smectite), kaolinite, quartz and dolomite, with high contents of silica (37.4%), alumina (17.2%), calcium oxide (5.7%) and iron oxide (7.5%). The CEC value obtained (41.0 meq 100 g -1 ), is due to the presence of kaolinite, which was confirmed by XRD, DTA-TG/DTG and FTIR results. BET and B.J.H. models showed that it is a mesoporous clay mineral, with a surface area of 84.81 m 2 g -1 . The surface charge measurement by Zeta Potential showed that this clay mineral is negatively charged in almost all of pH range studied. Thus, it has high adsorptive potential of drugs cationic species, while activation with sodium carbonate associated with organophilization process allow its application as oil drilling fluid.
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- 2021
28. DNA methylation profiling of CD04+/CD08+ T cells reveals pathogenic mechanisms in increasing hyperglycemia: PIRAMIDE pilot study
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Marco Salvatore, Teresa Infante, Linda Sommese, Celestino Sardu, Raffaele Marfella, Claudio Napoli, Concetta Schiano, Monica Franzese, Gelsomina Mansueto, Mario Zanfardino, Giovanni Francesco Nicoletti, Marco Miceli, Giuseppe Paolisso, Giuditta Benincasa, and Ornella Affinito
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medicine.medical_specialty ,Cholesterol ,business.industry ,General Medicine ,Methylation ,Type 2 diabetes ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Differentially methylated regions ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,Internal medicine ,DNA methylation ,medicine ,Biomarker (medicine) ,030211 gastroenterology & hepatology ,Surgery ,Prediabetes ,business ,Homeostasis - Abstract
Background DNA methylation can play a pathogenic role in the early stages of hyperglycemia linking homeostasis imbalance and vascular damage. Material and methods We investigated DNA methylome by RRBS in CD04+ and CD08+ T cells from healthy subjects (HS) to pre-diabetics (Pre-Diab) and type 2 diabetic (T2D) patients to identify early biomarkers of glucose impairment and vascular damage. Our cross-sectional study enrolled 14 individuals from HS state to increasing hyperglycemia (pilot study, PIRAMIDE trial, NCT03792607). Results Globally, differentially methylated regions (DMRs) were mostly annotated to promoter regions. Hypermethylated DMRs were greater than hypomethylated in CD04+ T cells whereas CD08+ T showed an opposite trend. Moreover, DMRs overlapping between Pre-Diab and T2D patients were mostly hypermethylated in both T cells. Interestingly, SPARC was the most hypomethylated gene in Pre-Diab and its methylation level gradually decreased in T2D patients. Besides, SPARC showed a significant positive correlation with DBP (+0.76), HDL (+0.54), Creatinine (+0.83), LVDd (+0.98), LVSD (+0.98), LAD (+0.98), LVPWd (+0.84), AODd (+0.81), HR (+0.72), Triglycerides (+0.83), LAD (+0.69) and AODd (+0.52) whereas a negative correlation with Cholesterol (−0.52) and LDL (−0.71) in T2D. Conclusion SPARC hypomethylation in CD08+ T cells may be a useful biomarker of vascular complications in Pre-Diab with a possible role for primary prevention warranting further multicenter clinical trials to validate our findings.
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- 2020
29. (+)-(E)-Chrysanthenyl Acetate: A Molecule with Interesting Biological Properties Contained in the Anthemis secundiramea (Asteraceae) Flowers
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Natale Badalamenti, Adriana Basile, Mario Varcamonti, Anna Zanfardino, Michela Di Napoli, Maurizio Bruno, Viviana Maresca, Michela Di Napoli, Viviana Maresca, Mario Varcamonti, Maurizio Bruno, Natale Badalamenti, Adriana Basile, Anna Zanfardino, Di Napoli, M., Maresca, V., Varcamonti, M., Bruno, M., Badalamenti, N., Basile, A., and Zanfardino, A.
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chrysanthenyl acetate ,Antibacterial and antioxidant activitie ,Antioxidant ,medicine.medical_treatment ,Anthemis secundiramea ,01 natural sciences ,lcsh:Technology ,essential oil ,lcsh:Chemistry ,Nutraceutical ,Botany ,medicine ,General Materials Science ,antibacterial and antioxidant activities ,Instrumentation ,essential oils ,lcsh:QH301-705.5 ,Fluid Flow and Transfer Processes ,biology ,010405 organic chemistry ,Chemistry ,lcsh:T ,Process Chemistry and Technology ,fungi ,General Engineering ,Biofilm ,food and beverages ,Asteraceae ,Antimicrobial ,biology.organism_classification ,Chrysanthenyl acetate ,lcsh:QC1-999 ,0104 chemical sciences ,Computer Science Applications ,010404 medicinal & biomolecular chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,lcsh:TA1-2040 ,lcsh:Engineering (General). Civil engineering (General) ,Bacteria ,lcsh:Physics - Abstract
Anthemis secundiramea is a perennial herb native widespread throughout the Mediterranean basin. The oil obtained from the flowers of this plant has antimicrobial properties against gram-positive and -negative bacteria, and inhibits the biofilm formation. The extract of A. secundiramea also has antioxidant activity&mdash, increasing the activity of different enzymes (SOD, CAT, and GPx). Surprisingly, in the oil extracted from the flowers, there is a single molecule, called (+)-(E)-chrysanthenyl acetate: This makes the A. secundiramea flowers extract extremely interesting for future topical, cosmetic, and nutraceutical applications.
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- 2020
30. Can COVID 2019 disease induce a specific cardiovascular damage or it exacerbates pre-existing cardiovascular diseases?
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Gelsomina Mansueto, Massimo Niola, Claudio Napoli, Mansueto, G., Niola, M., Napoli, C., Mansueto, G, Niola, M, and Napoli, C
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0301 basic medicine ,ARDS ,Myocarditis ,Endothelium ,Pneumonia, Viral ,Cardiovascular System ,Article ,Pathology and Forensic Medicine ,Renin-Angiotensin System ,Betacoronavirus ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immune system ,Humans ,Medicine ,Endothelial dysfunction ,Diffuse alveolar damage ,Pandemics ,Heme ,Lung ,Betacoronaviru ,Pandemic ,business.industry ,Coronavirus Infection ,SARS-CoV-2 ,COVID 2019 ,COVID-19 ,Cell Biology ,medicine.disease ,Cardiovascular disease ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Cardiovascular Diseases ,030220 oncology & carcinogenesis ,Immunology ,Autopsy ,Coronavirus Infections ,business ,Human - Abstract
Highlights • SARS-CoV-2 causes acute respiratory distress syndrome (ARDS) and multiple organ failure until death. • Myocarditis, acute myocardial infarction, arrhythmias thromboembolism, and disseminated intravascular coagulation (DIC) are the main complications in patients with cardiovascular comorbidities. • SARSCoV-2 can worsen the clinical status of patients with comorbidities especially pre-existing cardiovascular diseases and this may interfere with therapies., A novel coronavirus SARS-CoV-2 causes acute respiratory distress syndrome (ARDS) with cardiovascular and multiple organ failure till death. The main mechanisms of virus internalization and interaction with the host are down-regulation or upregulation of the ACE2 receptor, the surface glycoprotein competition mechanism for the binding of porphyrin to iron in heme formation as well as interference with the immune system. The interference on renin–angiotensin–aldosterone system (RAAS) activation, heme formation, and the immune response is responsible for infection diffusion, endothelial dysfunction, vasoconstriction, oxidative damage and releasing of inflammatory mediators. The main pathological findings are bilateral interstitial pneumonia with diffuse alveolar damage (DAD). Because ACE receptor is also present in the endothelium of other districts as well as in different cell types, and as porphyrins are transporters in the blood and other biological liquids of iron forming heme, which is important in the assembly of the hemoglobin, myoglobin and the cytochromes, multiorgan damage occurs both primitive and secondary to lung damage. More relevantly, myocarditis, acute myocardial infarction, thromboembolism, and disseminated intravasal coagulation (DIC) are described as complications in patients with poor outcome. Here, we investigated the role of SARSCoV-2 on the cardiovascular system and in patients with cardiovascular comorbidities, and possible drug interference on the heart.
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- 2020
31. A community-built calibration system: The case study of quantification of metabolites in grape juice by qNMR spectroscopy
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Ales Čamra, John Warren, Taylor David, Dinesh Chalasani, Daniele Ragno, Jan Teipel, Tommaso Di Noia, Aurimas Bieliauskas, Elina Zailer-Hafer, Stefano Todisco, Domenico Acquotti, Lorraine M. Bateman, James Donarski, Piero Mastrorilli, Rosa Ragone, Cristina Airoldi, John S. Harwood, Michael Assfalg, Dolores Molero Vilchez, Francesco Longobardi, Magali Martin-Biran, Elisabetta Schievano, Domenico Mallamace, Elisabetta Torregiani, Biagia Musio, Stefania Pontrelli, Paolo Dambruoso, Marina Veronesi, Livio Stevanato, Augusta Caligiani, Erwann Hamon, Maurizio Triggiani, Davide Bertelli, Flaminia Cesare Marincola, Stefano Mammi, Bernd Diehl, Vito Gallo, Daniela Valensin, Bhavaraju Sitaram, Alessandro Barge, Claudia Di Napoli, Elena Sáez Barajas, Pasquale Scapicchio, Emanuela Callone, Antonino Rizzuti, Panteleimon G. Takis, Fabio Bertocchi, Anna Borioni, Cristiano Zuccaccia, Maria Cecilia Rossi, Mario Latronico, Andrea Kobrlová, Luca Goldoni, Nicola Intini, Freddy Thomas, Roberto Gobetto, Renzo Luisi, Ana M. Gil, Pierluigi Mazzei, Julien Wist, Roberto Consonni, Francesca Benevelli, Algirdas Šačkus, Antonio Randazzo, Salvatore Milone, Archimede Rotondo, Roger J. Mulder, Silvia Davalli, Andrea Mele, Musio, B, Ragone, R, Todisco, S, Rizzuti, A, Latronico, M, Mastrorilli, P, Pontrelli, S, Intini, N, Scapicchio, P, Triggiani, M, Di Noia, T, Acquotti, D, Airoldi, C, Assfalg, M, Barge, A, Bateman, L, Benevelli, F, Bertelli, D, Bertocchi, F, Bieliauskas, A, Borioni, A, Caligiani, A, Callone, E, Čamra, A, Cesare Marincola, F, Chalasani, D, Consonni, R, Dambruoso, P, Davalli, S, David, T, Diehl, B, Donarski, J, Gil, A, Gobetto, R, Goldoni, L, Hamon, E, Harwood, J, Kobrlová, A, Longobardi, F, Luisi, R, Mallamace, D, Mammi, S, Martin-Biran, M, Mazzei, P, Mele, A, Milone, S, Molero Vilchez, D, Mulder, R, Napoli, C, Ragno, D, Randazzo, A, Rossi, M, Rotondo, A, Šačkus, A, Sáez Barajas, E, Schievano, E, Sitaram, B, Stevanato, L, Takis, P, Teipel, J, Thomas, F, Torregiani, E, Valensin, D, Veronesi, M, Warren, J, Wist, J, Zailer-Hafer, E, Zuccaccia, C, Gallo, V, Musio, B., Ragone, R., Todisco, S., Rizzuti, A., Latronico, M., Mastrorilli, P., Pontrelli, S., Intini, N., Scapicchio, P., Triggiani, M., Di Noia, T., Acquotti, D., Airoldi, C., Assfalg, M., Barge, A., Bateman, L., Benevelli, F., Bertelli, D., Bertocchi, F., Bieliauskas, A., Borioni, A., Caligiani, A., Callone, E., Camra, A., Cesare Marincola, F., Chalasani, D., Consonni, R., Dambruoso, P., Davalli, S., David, T., Diehl, B., Donarski, J., Gil, A. M., Gobetto, R., Goldoni, L., Hamon, E., Harwood, J. S., Kobrlova, A., Longobardi, F., Luisi, R., Mallamace, D., Mammi, S., Martin-Biran, M., Mazzei, P., Mele, A., Milone, S., Molero Vilchez, D., Mulder, R. J., Napoli, C., Ragno, D., Randazzo, A., Rossi, M. C., Rotondo, A., Sackus, A., Saez Barajas, E., Schievano, E., Sitaram, B., Stevanato, L., Takis, P. G., Teipel, J., Thomas, F., Torregiani, E., Valensin, D., Veronesi, M., Warren, J., Wist, J., Zailer-Hafer, E., Zuccaccia, C., and Gallo, V.
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Analyte ,Magnetic Resonance Spectroscopy ,Traceability ,qNMR Interlaboratory comparison Calibration Multiple regression Validation Food quality control ,02 engineering and technology ,01 natural sciences ,Analytical Chemistry ,NO ,Food quality control ,Matrix (chemical analysis) ,Interlaboratory comparison ,Validation ,CHIM/06 - CHIMICA ORGANICA ,Calibration ,Calibration, Food quality control, Interlaboratory comparison, Multiple regression, qNMR, Validation ,Vitis ,qNMR ,Multiple regression ,qNMR, Interlaboratory comparison, Calibration, Multiple regression, Validation, Food quality control ,Spectroscopy ,Fruit and Vegetable Juices ,Reproducibility ,Spectrometer ,Chemistry ,010401 analytical chemistry ,Analytical technique ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,qNMR, interlaboratory comparison ,Fruit and Vegetable Juice ,0210 nano-technology ,Biological system - Abstract
Nuclear Magnetic Resonance (NMR) is an analytical technique extensively used in almost every chemical laboratory for structural identification. This technique provides statistically equivalent signals in spite of using spectrometer with different hardware features and is successfully used for the traceability and quantification of analytes in food samples. Nevertheless, to date only a few internationally agreed guidelines have been reported on the use of NMR for quantitative analysis. The main goal of the present study is to provide a methodological pipeline to assess the reproducibility of NMR data produced for a given matrix by spectrometers from different manufacturers, with different magnetic field strengths, age and hardware configurations. The results have been analyzed through a sequence of chemometric tests to generate a community-built calibration system which was used to verify the performance of the spectrometers and the reproducibility of the predicted sample concentrations.
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- 2020
32. mtDNA depletion‐like syndrome in Wilson disease
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Gaurav V. Sarode, Janine M. LaSalle, Tagreed A. Mazi, Gyu-Young Song, Cecilia R Giulivi, Tomasz Litwin, Anna Członkowska, Charles E. Mordaunt, Eleonora Napoli, Dorothy A. Kieffer, Andre Oliveira Guimarães, Noreene M. Shibata, and Valentina Medici
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Mitochondrial DNA ,Oxidative phosphorylation ,Mitochondrion ,medicine.disease_cause ,DNA, Mitochondrial ,Article ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Hepatolenticular Degeneration ,medicine ,Animals ,Humans ,Citrate synthase ,Hepatology ,DNA synthesis ,biology ,Chemistry ,Penicillamine ,Molecular biology ,Liver ,Copper-Transporting ATPases ,030220 oncology & carcinogenesis ,biology.protein ,030211 gastroenterology & hepatology ,Copper ,DNA ,Oxidative stress ,medicine.drug - Abstract
BACKGROUND & AIMS: Wilson disease is caused by mutations in the copper transporter ATP7B, with its main pathology attributed to copper-mediated oxidative damage. The limited therapeutic effect of copper chelators and the early occurrence of mitochondrial deficits, however, undermine the prevalence of this mechanism. METHODS: We characterized mitochondrial DNA copy number and mutations as well as bioenergetic deficits in blood from patients with WD and in livers of tx-j mice, a mouse model of hepatic copper accumulation. In vitro experiments with hepatocytes treated with CuSO(4) were conducted to validate in vivo studies. RESULTS: Here, for the first time, we characterized the bioenergetic deficits in Wilson disease as consistent with a mitochondrial DNA depletion-like syndrome. This is evidenced by enriched DNA synthesis/replication pathways in serum metabolomics and decreased mitochondrial DNA copy number in blood of Wilson disease patients as well as decreased mitochondrial DNA copy number, increased citrate synthase activity, and selective Complex IV deficit in livers of the tx-j mouse model of Wilson disease. Tx-j mice treated with the copper chelator penicillamine, methyl donor choline, or both ameliorated mitochondrial DNA damage but further decreased mitochondrial DNA copy number. Experiments with copper-loaded HepG2 cells validated the concept of a direct copper-mitochondrial DNA interaction. CONCLUSIONS: This study underlines the relevance of targeting the copper-mitochondrial DNA pool in the treatment of Wilson disease separate from the established copper-induced oxidative stress-mediated damage.
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- 2020
33. Sensorial analysis of commercial quality of lettuce grown on different substrates
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Nítalo André Farias Machado, Francisco Ivo dos Santos Aguiar, Maryzélia Furtado de Farias, A. Napoli, S. S. Matos, C. S. Reis, and L. J. Parra-Serrano
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lcsh:A ,biochar, babassu, chicken bed litter, lactuca sativa l., organic fertilization ,engineering.material ,Latosol ,Sensory analysis ,Attalea speciosa ,Nutrient ,Biochar ,Multicriteria analysis ,Q04 - Composition des produits alimentaires ,Engrais organique ,Chemistry ,Lactuca sativa ,Sowing ,Qualité des aliments ,Horticulture ,Analyse organoleptique ,engineering ,Fertilizer ,lcsh:General Works ,Organic fertilizer ,F04 - Fertilisation - Abstract
Regional residues of agricultural, livestock and forestry activities can be used in the formulation of substrates that allow the adequate supply of nutrients in family agricultural production. The objective of this research was to determine the efficiency of different formulations of substrates enriched with babassu biochar for the commercial development of lettuce through sensorial analysis. The experiment was conducted in the period from November 2016 to February 2017. The design was completely randomized, with nine treatments and 15 replicates. Dystrophic Yellow Latosol (dYL), increasing doses of biochar (B); organic fertilizer (OF) and mineral fertilizer (MF) were used in the substrate preparation. The treatments evaluated were: S1 = dYL, S2 = dYL +10 t ha-1B, S3 = dYL +20 t ha-1B, S4 = dYL 30 t ha-1 B, S5 = dYL + 2 t ha-1 OF, S6 = dYL + 5 t ha-1 OF, S7 = dYL +8 t ha-1 OF, S8 = dYL +10 t ha-1 B + 2 t ha-1 OF, S9 = dYL + MF. At 80 days after sowing, sensory analyzes were carried out in order to judge the visual characteristics of the lettuce per treatment. Based on the multicriteria analysis the S4 substrate, the one that contain 30 t ha-1 of biochar proved to be the most successful substrate to comply with the study variables. Thus, the use of biochar can be considered as a viable alternative to mineral fertilizer in terms of sensory analysis.
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- 2020
34. MYB–bHLH–TTG1 Regulates Arabidopsis Seed Coat Biosynthesis Pathways Directly and Indirectly via Multiple Tiers of Transcription Factors
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Song Feng Li, Ross S Napoli, Hanh Pham, Roger W. Parish, Patrick J Allen, and Richard G Browne
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Physiology ,Arabidopsis ,Repressor ,Cyclopentanes ,Plant Science ,Lignin ,Models, Biological ,Plant Epidermis ,Membrane Lipids ,Plant Mucilage ,chemistry.chemical_compound ,Gene Expression Regulation, Plant ,Arabidopsis thaliana ,Plant Immunity ,MYB ,Oxylipins ,Promoter Regions, Genetic ,Gene ,Base Sequence ,biology ,Arabidopsis Proteins ,Jasmonic acid ,Promoter ,Cell Biology ,General Medicine ,biology.organism_classification ,Biosynthetic Pathways ,Cell biology ,Repressor Proteins ,Metabolic pathway ,chemistry ,Waxes ,Seeds ,Tannins ,Abscisic Acid ,Signal Transduction ,Transcription Factors - Abstract
MYB–bHLH–WDR (MBW) transcription factor (TF) complexes regulate Arabidopsis seed coat development including mucilage and tannin biosynthesis. The R2R3 MYBs MYB5, MYB23 and TRANSPARENT TESTA2 (TT2) participate in the MBW complexes with the WD-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1). These complexes regulate GLABRA2 (GL2) and TTG2 expression in developing seeds. Microarray transcriptome analysis of ttg1-1- and wild-type (Ler) developing seeds identified 246 TTG1-regulated genes, which include all known metabolic genes of the tannin biosynthetic pathway. The first detailed TTG1-dependent metabolic pathways could be proposed for the biosynthesis of mucilage, jasmonic acid (JA) and cuticle including wax ester in developing seeds. We also assigned many known and previously uncharacterized genes to the activation/inactivation of hormones, plant immunity and nutrient transport. The promoters of six cuticle pathway genes were active in developing seeds. Expression of 11 genes was determined in the developing seeds of the combinatorial mutants of MYB5, MYB23 and TT2, and in the combinatorial mutants of GL2, HOMEODOMAIN GLABROUS2 (HDG2) and TTG2. These six TFs positively co-regulated the expression of four repressor genes while three of the six TFs repressed the wax biosynthesis genes examined, suggesting that the three TFs upregulate the expression of these repressor genes, which, in turn, repress the wax biosynthesis genes. Chromatin immunoprecipitation analysis identified 21 genes directly regulated by MYB5 including GL2, HDG2, TTG2, four repressor genes and various metabolic genes. We propose a multi-tiered regulatory mechanism by which MBWs regulate tannin, mucilage, JA and cuticle biosynthetic pathways.
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- 2020
35. Over-liming in the Construction of the Fertility of Red Yellow Latosol with Different Phosphorus Sources
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Gilson Araújo de Freitas, Bruno Henrique Di Napoli Nunes, João Henrique Silva da Luz, Jessiane da Silva Carvalho, Hanrara Pires de Oliveira, Lara Couto Marques, Rubens Ribeiro da Silva, Evandro Alves Ribeiro, and Gilson do Carmo Alexandrino
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Agronomy ,Chemistry ,media_common.quotation_subject ,Phosphorus ,chemistry.chemical_element ,Fertility ,General Medicine ,Latosol ,media_common - Abstract
The availability of P in Cerrado soils is a limiting factor for the satisfactory development of crops. It is known that the efficiency of phosphate fertilization is low and depends on several factors, such as solubility of fertilizers, soil texture, and soil acidity. Thus, the objective of this work was to evaluate the availability of phosphorus as a function of different phosphate sources under the influence of pH, as well as to determine its fertilization efficiency in a red latosol. The experiment was carried out in a greenhouse at Tocantins federal university, in DIC, Brazil was used, in a 3 x 5 + 1 scheme. A red-yellow Latosol was used and three sources of phosphate fertilization were evaluated: Mono-ammonic phosphate - MAP, single superphosphate - SS and Natural phosphate - FN, plus one treatment without fertilization, in five evaluation periods (0, 7, 14, 21 and 28 days). Therefore, the pH in CaCl2 of the soil stabilized between (5.5 – 6.5) in approximately 83 days of incubation with the acidity concealer. The SS and MAP phosphate fertilizers promoted the highest available P contents, with 6.32 and 6.23 mg.d m−3, respectively. The use of FN showed low P levels during the evaluated incubation period, mainly due to its lower solubility.
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- 2020
36. Drp1 overexpression induces desmin disassembling and drives kinesin-1 activation promoting mitochondrial trafficking in skeletal muscle
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Paulina Roux-Biejat, Sara Barozzi, Emilio Clementi, Claudia Moscheni, Cristiana Perrotta, Michela Ripolone, Marco Coazzoli, Chiara Vantaggiato, Massimiliano Garrè, Matteo Giovarelli, Dario Parazzoli, Emanuele Martini, Silvia Zecchini, Davide Cervia, Clara De Palma, and Laura Napoli
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Dynamins ,endocrine system ,Cell biology ,Kinesins ,macromolecular substances ,Mitochondrion ,Biochemistry ,Microtubules ,Article ,Desmin ,DNM1L ,Phosphoserine ,CDC2 Protein Kinase ,medicine ,Myocyte ,Animals ,Humans ,Phosphorylation ,Muscle, Skeletal ,Molecular Biology ,Mitochondrial transport ,Quinazolinones ,Chemistry ,Skeletal muscle ,Transport protein ,Mitochondria ,Enzyme Activation ,Mice, Inbred C57BL ,Succinate Dehydrogenase ,Protein Transport ,medicine.anatomical_structure ,Kinesin - Abstract
Mitochondria change distribution across cells following a variety of pathophysiological stimuli. The mechanisms presiding over this redistribution are yet undefined. In a murine model overexpressing Drp1 specifically in skeletal muscle, we find marked mitochondria repositioning in muscle fibres and we demonstrate that Drp1 is involved in this process. Drp1 binds KLC1 and enhances microtubule-dependent transport of mitochondria. Drp1-KLC1 coupling triggers the displacement of KIF5B from kinesin-1 complex increasing its binding to microtubule tracks and mitochondrial transport. High levels of Drp1 exacerbate this mechanism leading to the repositioning of mitochondria closer to nuclei. The reduction of Drp1 levels decreases kinesin-1 activation and induces the partial recovery of mitochondrial distribution. Drp1 overexpression is also associated with higher cyclin-dependent kinase-1 (Cdk-1) activation that promotes the persistent phosphorylation of desmin at Ser-31 and its disassembling. Fission inhibition has a positive effect on desmin Ser-31 phosphorylation, regardless of Cdk-1 activation, suggesting that induction of both fission and Cdk-1 are required for desmin collapse. This altered desmin architecture impairs mechanotransduction and compromises mitochondrial network stability priming mitochondria transport through microtubule-dependent trafficking with a mechanism that involves the Drp1-dependent regulation of kinesin-1 complex.
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- 2020
37. Epigenetic-based therapy in allogenic hematopoietic stem cell transplantation: Novel opportunities for personalized treatment
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Alessio Corrado, Claudio Napoli, Antonietta Picascia, Maria Vasco, Annunziata Sansone, Giuditta Benincasa, Benincasa, G., Vasco, M., Corrado, A., Sansone, A., Picascia, A., and Napoli, C.
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Oncology ,medicine.medical_specialty ,immunosuppressant ,medicine.medical_treatment ,Azacitidine ,Decitabine ,Graft vs Host Disease ,chemical and pharmacologic phenomena ,Hematopoietic stem cell transplantation ,030230 surgery ,Epigenesis, Genetic ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Panobinostat ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Precision Medicine ,Vorinostat ,Transplantation ,business.industry ,clinical epigenetic ,donors and donation: donor follow-up ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,clinical trial ,medicine.disease ,Clinical trial ,surgical procedures, operative ,Graft-versus-host disease ,chemistry ,030211 gastroenterology & hepatology ,rejection ,business ,medicine.drug ,clinical immunology - Abstract
Current management of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) lacks immunosuppressant drugs able to block the host immune response toward the graft antigens. Novel treatments may include epigenetic compounds (epidrugs) some of which have been yet approved by the Food and Drugs Administration for the treatment of specific blood malignancies. The most investigated in clinical trials for allo-HSCT are DNA demethylating agents (DNMTi), such as azacitidine (Vidaza) and decitabine (Dacogen) as well as histone deacetylases inhibitors (HDACi), such as vorinostat (Zolinza) and panobinostat (Farydak). Indeed, azacitidine monotherapy before allo-HSCT may reduce the conventional chemotherapy-related complications, whereas it may reduce relapse risk and death after allo-HSCT. Besides, a decitabine-containing conditioning regimen could protect against graft versus host disease (GVHD) and respiratory infections after allo-HSCT. Regarding HDACi, the addition of vorinostat and panobinostat to the conditioning regimen after allo-HSCT seems to reduce the incidence of acute GVHD. Furthermore, panobinostat alone or in combination with low-dose decitabine may reduce the relapse rate in high-risk patients with acute myeloid leukemia patients after allo-HSCT. We discuss the phase 1 and 2 clinical trials evaluating the possible beneficial effects of repurposing specific epidrugs which may guide personalized therapy in the setting of allo-HSCT.
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- 2021
38. Immune reactivity during COVID-19: Implications for treatment
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Clelia Criscuolo, Cinzia Liberato, Mariangela Rusciano, Claudio Napoli, Giuditta Benincasa, Mario Faenza, Napoli, C., Benincasa, G., Criscuolo, C., Faenza, M., Liberato, C., and Rusciano, M.
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0301 basic medicine ,ARDS ,medicine.disease_cause ,Severity of Illness Index ,immune response ,chemistry.chemical_compound ,Immunosuppressive Agent ,0302 clinical medicine ,Glucocorticoid ,Eosinopenia ,Immunology and Allergy ,Hospital Mortality ,Randomized Controlled Trials as Topic ,Immunoglobulins, Intravenous ,Immunosenescence ,Prognosis ,drug therapy ,Treatment Outcome ,Drug Therapy, Combination ,Immunotherapy ,Cytokine Release Syndrome ,Immunosuppressive Agents ,Human ,Prognosi ,Immunology ,macromolecular substances ,Antibodies, Monoclonal, Humanized ,Article ,03 medical and health sciences ,Tocilizumab ,Immune system ,medicine ,Humans ,Glucocorticoids ,COVID-19 Serotherapy ,business.industry ,SARS-CoV-2 ,Anticoagulant ,Drug Repositioning ,Immunization, Passive ,COVID-19 ,Anticoagulants ,laboratory indexes ,Immune dysregulation ,medicine.disease ,COVID-19 Drug Treatment ,030104 developmental biology ,chemistry ,Macrophage activation syndrome ,Immunoglobulins, Intravenou ,laboratory indexe ,Cytokine storm ,business ,030215 immunology - Abstract
Highlights • Lymphopenia and eosinopenia are associated with the severe form of COVID-19. • Increased levels of D-dimer, procalcitonin, and C reactive protein are prognostic biomarkers predicting coagulopathy. • Corticosteroids resulted the best therapy for the immune dysregulation in severe form of COVID-19. • Anticoagulative therapy is associated with reduced in-hospital mortality for COVID-19., Clinical symptoms of COVID-19 include fever, cough, and fatigue which may progress to acute respiratory distress syndrome (ARDS). The main hematological laboratory findings associated with the severe form of disease are represented by lymphopenia and eosinopenia which mostly occur in the elderly population characterized by cardiovascular comorbidities and immunosenescence. Besides, increased levels of D-dimer, procalcitonin, and C reactive protein (CRP) seem to be powerful prognostic biomarkers helping to predict the onset of coagulopathy. The host immune response to SARS-CoV-2 can lead to an aberrant inflammatory response or “cytokine storm” which contributes to the severity of illness. At immunological level, patients affected by a severe form of COVID-19 show poor clinical trajectories characterized by differential “immunotypes” for which T cell response seems to play a critical role in understanding pathogenic mechanisms of disease. Also, patients with mild to severe COVID-19 displayed macrophage activation syndrome (MAS), very low human leukocyte antigen D related (HLA-DR) expression with a parallel reduction of CD04+ lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Corticosteroids resulted the best therapy for the immune dysregulation whereas repurposing of tocilizumab (IL-6 receptor antagonist) appears to have mixed results in patients with COVID-19. Besides, anticoagulative therapy was associated with reduced in-hospital mortality and need of intubation among COVID-19 patients. Furthermore, the beneficial use of intravenous immunoglobulin (IVIG) and passive immunotherapy with convalescent plasma needs to be validated in large controlled clinical trials. In this review, we summarize the main hematological parameters with a prognostic value in COVID-19 and the basis of immunological reactivity during COVID-19, with a focus on ongoing clinical trials evaluating immune targets as possible therapeutic strategies.
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- 2021
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39. Silver (I) N-Heterocyclic Carbene Complexes: A Winning and Broad Spectrum of Antimicrobial Properties
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Giuseppe Felice Mangiatordi, Mario Varcamonti, Stefano D'Errico, Anna Zanfardino, Filippo Prencipe, Michele Saviano, Gennaro Piccialli, Filomena Rossi, Luisa Ronga, Michela Di Napoli, Diego Tesauro, Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Naples, Prencipe, F., Zanfardino, A., Di Napoli, M., Rossi, F., D'Errico, S., Piccialli, G., Mangiatordi, G. F., Saviano, M., Ronga, L., Varcamonti, M., and Tesauro, D.
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Silver ,antimicrobial properties ,Pyrazole ,010402 general chemistry ,01 natural sciences ,Article ,Catalysis ,Inorganic Chemistry ,lcsh:Chemistry ,chemistry.chemical_compound ,Heterocyclic Compounds ,[CHIM]Chemical Sciences ,Molecule ,Humans ,Gram‐positive and negative bacteria ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Bacteria ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Cationic polymerization ,General Medicine ,Chromophore ,Antimicrobial ,Combinatorial chemistry ,3. Good health ,0104 chemical sciences ,Computer Science Applications ,Anti-Bacterial Agents ,Gram-positive and negative bacteria ,Antimicrobial propertie ,HEK293 Cells ,NHC silver complexes ,lcsh:Biology (General) ,lcsh:QD1-999 ,Acridine ,Carbene ,Methane - Abstract
International audience; The evolution of antibacterial resistance has arisen as the main downside in fighting bacterial infections pushing researchers to develop novel, more potent and multimodal alternative drugs.Silver and its complexes have long been used as antimicrobial agents in medicine due to the lack of silver resistance and the effectiveness at low concentration as well as to their low toxicities compared to the most commonly used antibiotics. N-Heterocyclic Carbenes (NHCs) have been extensively employed to coordinate transition metals mainly for catalytic chemistry. However, more recently, NHC ligands have been applied as carrier molecules for metals in anticancer applications. In the present study we selected from literature two NHC-carbene based on acridinescaffoldand detailed nonclassicalpyrazole derived mono NHC-Ag neutral and bis NHC-Ag cationic complexes. Their inhibitor effect on bacterial strains Gram-negative and positivewas evaluated. Imidazolium NHC silver complex containing the acridine chromophore showed effectiveness at extremely low MIC values. Although pyrazole NHC silver complexes are less active than the acridine NHC-silver, they represent the first example of this class of compounds with antimicrobial properties. Moreover all complexesare not toxic and they show not significant activity againstmammalian cells (Hek lines) after 4 and 24 h. Based on our experimental evidence, we are confident that this promising class of complexes could represent a valuable starting point for developing candidates for the treatment of bacterial infections, delivering great effectiveness and avoiding the development of resistance mechanisms.
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- 2021
40. Impact of micro and macroporous TFF membranes on product sieving and chromatography loading for perfusion cell culture
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Nuno D.S. Pinto, William N. Napoli, and Mark Brower
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0106 biological sciences ,0301 basic medicine ,Cell Culture Techniques ,Bioengineering ,CHO Cells ,01 natural sciences ,Applied Microbiology and Biotechnology ,law.invention ,Cross-flow filtration ,03 medical and health sciences ,Bioreactors ,Cricetulus ,law ,Cricetinae ,010608 biotechnology ,Bioreactor ,Animals ,Filtration ,Chromatography ,Chemistry ,Antibodies, Monoclonal ,Membranes, Artificial ,Equipment Design ,Microporous material ,Permeation ,030104 developmental biology ,Membrane ,Depth filter ,Chromatography column ,Chromatography, Liquid ,Biotechnology - Abstract
Bioprocess intensification can be achieved through high cell density perfusion cell culture with continuous protein capture integration. Protein passage and cell retention are commonly accomplished using tangential flow filtration systems consisting of microporous membranes. Significant challenges, including low efficiency and decaying product sieving over time, are commonly observed in these cell retention devices. Here, we demonstrate that a macroporous membrane overcomes the product sieving challenges when comparing to several other membrane chemistries and pore sizes within the microporous range. This way, variable chromatography column loading is avoided. The macroporous membrane yielded a 13,000 L/m2 volumetric throughput. The membrane's cut-off size results in an increased permeate turbidity due to particles passage, such as cell debris, through pores ranging from 1 to 4 µm. In addition, successful chromatography column plugging mitigation was achieved by employing depth filtration before the chromatographic step. Depth filtration volumetric throughputs were between 600 and 1,000 L/m2 . Combing a macroporous cell retention device with a depth filter not only provided an alternative to address the challenge of undesired long protein residence times in the bioreactor due to product sieving decay, but also exhibited a throughput increase, making the integration of multicolumn capture chromatography with a perfusion cell culture a more robust process.
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- 2019
41. Retinal Plasticity
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Enrica Strettoi, Beatrice Di Marco, Noemi Orsini, and Debora Napoli
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Neuronal Plasticity ,QH301-705.5 ,Organic Chemistry ,Cell Plasticity ,deafferentation ,General Medicine ,structural plasticity ,Catalysis ,Retina ,Computer Science Applications ,Inorganic Chemistry ,Chemistry ,retinitis pigmentosa ,Animals ,Humans ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,remodeling ,Retinal Neurons - Abstract
Brain plasticity is a well-established concept designating the ability of central nervous system (CNS) neurons to rearrange as a result of learning, when adapting to changeable environmental conditions or else while reacting to injurious factors. As a part of the CNS, the retina has been repeatedly probed for its possible ability to respond plastically to a variably altered environment or to pathological insults. However, numerous studies support the conclusion that the retina, outside the developmental stage, is endowed with only limited plasticity, exhibiting, instead, a remarkable ability to maintain a stable architectural and functional organization. Reviewed here are representative examples of hippocampal and cortical paradigms of plasticity and of retinal structural rearrangements found in organization and circuitry following altered developmental conditions or occurrence of genetic diseases leading to neuronal degeneration. The variable rate of plastic changes found in mammalian retinal neurons in different circumstances is discussed, focusing on structural plasticity. The likely adaptive value of maintaining a low level of plasticity in an organ subserving a sensory modality that is dominant for the human species and that requires elevated fidelity is discussed.
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- 2021
42. Origanum vulgare ssp. hirtum (Lamiaceae) Essential Oil Prevents Behavioral and Oxidative Stress Changes in the Scopolamine Zebrafish Model
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Giuseppe Ruberto, Lucian Hritcu, Edoardo Napoli, and Luminita Capatina
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Antioxidant ,Aché ,Origanum vulgare ssp. hirtum ,medicine.medical_treatment ,Pharmaceutical Science ,Pharmacology ,medicine.disease_cause ,Neuroprotection ,Article ,essential oil ,Analytical Chemistry ,law.invention ,scopolamine ,memory ,chemistry.chemical_compound ,QD241-441 ,origanum vulgare spp. hirtum ,law ,Drug Discovery ,medicine ,oxidative stress ,Physical and Theoretical Chemistry ,Thymol ,Essential oil ,biology ,Organic Chemistry ,Origanum ,biology.organism_classification ,anxiety ,Acetylcholinesterase ,language.human_language ,chemistry ,Chemistry (miscellaneous) ,language ,Molecular Medicine ,oxidative stressa ,Oxidative stress - Abstract
Origanum vulgare ssp. hirtum has been used as medicinal herbs promoting antioxidant, anti-inflammatory, antimicrobial, and neuroprotective activities. We investigated the protective effects and the mechanism of O. vulgare ssp. hirtum essential oil (OEO) on cognitive impairment and brain oxidative stress in a scopolamine (Sco)-induced zebrafish (Danio rerio) model of cognitive impairment. Our results show that exposure to Sco (100 µM) leads to anxiety, spatial memory, and response to novelty dysfunctions, whereas the administration of OEO (25, 150, and 300 µL/L, once daily for 13 days) reduced anxiety-like behavior and improved cognitive ability, which was confirmed by behavioral tests, such as the novel tank-diving test (NTT), Y-maze test, and novel object recognition test (NOR) in zebrafish. Additionally, Sco-induced brain oxidative stress and increasing of acetylcholinesterase (AChE) activity were attenuated by the administration of OEO. The gas chromatography–mass spectrometry (GC-MS) analyses were used to elucidate the OEO composition, comprising thymol (38.82%), p-cymene (20.28%), and γ-terpinene (19.58%) as the main identified components. These findings suggest the ability of OEO to revert the Sco-induced cognitive deficits by restoring the cholinergic system activity and brain antioxidant status. Thus, OEO could be used as perspective sources of bioactive compounds, displaying valuable biological activities, with potential pharmaceutical applications.
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- 2021
43. Volcanic CO2 seep geochemistry and use in understanding ocean acidification
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Marco Milazzo, Jason M. Hall-Spencer, R. Di Napoli, Stefano Caliro, Alessandro Aiuppa, G. Turco, Aiuppa A., Hall-Spencer J.M., Milazzo M., Turco G., Caliro S., and Di Napoli R.
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0106 biological sciences ,Settore BIO/07 - Ecologia ,010504 meteorology & atmospheric sciences ,Geochemistry ,Marine life ,01 natural sciences ,chemistry.chemical_compound ,Algae ,Environmental Chemistry ,Submarine hydrothermalism ,Marine ecosystem ,0105 earth and related environmental sciences ,Earth-Surface Processes ,Water Science and Technology ,Calcifying species ,Carbon dioxide in Earth's atmosphere ,biology ,010604 marine biology & hydrobiology ,Natural analogues ,Coralline algae ,Ocean acidification ,biology.organism_classification ,Ecosystem effects ,Settore GEO/08 - Geochimica E Vulcanologia ,chemistry ,Carbon dioxide ,Environmental science ,Seawater - Abstract
Ocean acidification is one of the most dramatic effects of the massive atmospheric release of anthropogenic carbon dioxide (CO2) that has occurred since the Industrial Revolution, although its effects on marine ecosystems are not well understood. Submarine volcanic hydrothermal fields have geochemical conditions that provide opportunities to characterise the effects of elevated levels of seawater CO2 on marine life in the field. Here, we review the geochemical aspects of shallow marine CO2-rich seeps worldwide, focusing on both gas composition and water chemistry. We then describe the geochemical effects of volcanic CO2 seepage on the overlying seawater column. We also present new geochemical data and the first synthesis of marine biological community changes from one of the best-studied marine CO2 seep sites in the world (off Vulcano Island, Sicily). In areas of intense bubbling, extremely high levels of pCO2 (> 10,000 μatm) result in low seawater pH (2. Laboratory advances in our understanding of species sensitivity to high CO2 and low pH seawater, reveal how marine organisms react to simulated ocean acidification conditions (e.g., using energetic trade-offs for calcification, reproduction, growth and survival). Research at volcanic marine seeps, such as those off Vulcano, highlight consistent ecosystem responses to rising levels of seawater CO2, with the simplification of food webs, losses in functional diversity and reduced provisioning of goods and services for humans.
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- 2021
44. Increased illumination levels enhance biosynthesis of aloenin A and aloin B in Aloe arborescens Mill., but lower their per-plant yield
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Edoardo Napoli, Silvia Lazzara, Anna Concetta Cangemi, Alessandra Carrubba, Antonio Giovino, Alessandra Culmone, Lazzara S., Carrubba A., Napoli E., Culmone A., Cangemi A.C., and Giovino A.
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0106 biological sciences ,Aloe arborescens ,Aloin ,01 natural sciences ,chemistry.chemical_compound ,aloin ,Leaf size ,Dry matter ,biology ,010405 organic chemistry ,secondary metabolites ,Crop yield ,biology.organism_classification ,aloenin ,0104 chemical sciences ,Aloe arborescens, Aloenin, Aloin, Cultivation, Secondary metabolites, Shading ,Horticulture ,Light intensity ,chemistry ,cultivation ,Perlite ,Shading ,Agronomy and Crop Science ,shading ,010606 plant biology & botany - Abstract
Leaves of Aloe arborescens Mill. are a relevant source of secondary metabolites of pharmaceutical relevance. Notwithstanding, specialized cultivations of A. arborescens are still rather limited, and a straightforward agronomical research addressed to the obtainment of high-quality material is lacking. With the purpose to fill this gap, from 2016 to 2018, a trial was arranged to evaluate the growth and development of A. arborescens, along with the production of four active metabolites (aloin A and B, aloenin A, and isoaloeresin D) with varying some growth conditions. Two growth substrates (“A”- a commercial substrate, and “B”- the same substrate + 20 % perlite), two durations of pre-transplant open-air storage (“stress”, 7 and 14 days), and 3 illumination levels obtained by means of shadow nets with different mesh dimensions (SL: full sunlight; T50: 50 % shading; T70: 70 % shading) were tested, combined in a factorial experimental layout with 3 repetitions. In general, light intensity was the most crucial experimental factor, whereas the effects of growth substrate and pre-transplant stress were scarce and limited in time. The addition of perlite to the growth substrate gave the best results in terms of leaf size and root growth, without any significant effect on the yield of active metabolites. The increasing shading level caused a parallel increase of several biometrical characters of plants (height, number of leaves per plant and mean diameter of the stem), whereas the number of suckers per plant was positively affected by the increase of illumination level. The illumination level was also responsible for significant variations in the content of all secondary metabolites, except for aloin A, that resulted statistically not different among the illumination treatments (from 0.80 to 0.98 % in dry matter). The content of aloenin A and aloin B was higher in the plants exposed in full sun, statistically well differentiated from those exposed to 70 % shadow (2.0 vs. 1.4 % d.m. aloenin A, and 1.12 vs 0.86 % d.m. aloin B, in full sun and 70 % shadow, respectively). Contrastingly, the highest levels of isoaloeresin D were reached in the two shaded treatments (4.98 % in 50 % shadow and 4.89 % in 70 % shadow), whereas the full sun treatment reached the lowest value. The higher number of leaves in plants exposed at reduced illumination, however, brought to increased total amounts per plant of aloin (A and B) and aloenin A with increasing shadow levels.
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- 2021
45. Proteins of the fruit pulp of Acca sellowiana have antimicrobial activity directed against the bacterial membranes
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Mario Varcamonti, Viviana Maresca, Michela Di Napoli, Adriana Basile, Anna Zanfardino, Sergio Sorbo, di napoli, Michela, Maresca, Viviana, Sorbo, Sergio, Varcamonti, Mario, Basile, Adriana, and Zanfardino, Anna
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Low protein ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,food and beverages ,Plant Science ,Antimicrobial ,biology.organism_classification ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Analytical Chemistry ,010404 medicinal & biomolecular chemistry ,Membrane ,Mechanism of action ,Polyphenol ,medicine ,Pulp (tooth) ,Food science ,medicine.symptom ,Antibacterial activity ,Bacteria - Abstract
Acca sellowiana is an evergreen plant that produces edible fruit whit high nutritional properties, and also contains clinically relevant bioactive compounds, including polyphenols and essential oils. Numerous biological activities were demonstrated for A. sellowiana fruits: antifungal and antitumoral and anti-oxidant. It was also showed a strong antibacterial activity against Gram-positive and Gram-negative bacteria. Fruit are generally considered recalcitrant plant tissues for the difficulty to obtain high quality protein due to a low protein content and the presence of interfering substances. For this reason, the objective of the present work was obtain high quantity of protein extract, to determine the location in the fruit of the molecules responsible for the antibacterial activity, separate them according to molecular weight, test their thermo resistance, study the timing of action, isolate the protein fraction having activity and hypothesise a mechanism of action directed against bacterial membranes.
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- 2021
46. Diabetes and cognitive impairment: A role for glucotoxicity and dopaminergic dysfunction
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Paola Mirra, Antonella Desiderio, Francesca Chiara Pignalosa, Cecilia Nigro, Pietro Formisano, Luca Ulianich, Claudia Miele, Raffaele Napoli, Francesca Fiory, Giuseppe Perruolo, Francesco Beguinot, Pignalosa, F. C., Desiderio, A., Mirra, P., Nigro, C., Perruolo, G., Ulianich, L., Formisano, P., Beguinot, F., Miele, C., Napoli, R., and Fiory, F.
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Glycation End Products, Advanced ,Dopamine ,Review ,chemistry.chemical_compound ,Cognition ,Glycation ,Diabetes Complication ,Medicine ,Biology (General) ,Neurotransmitter ,Cognitive impairment ,Glucotoxicity ,Spectroscopy ,Methylglyoxal ,Dopaminergic ,General Medicine ,Pyruvaldehyde ,Computer Science Applications ,Chemistry ,diabetes mellitus ,Dopaminergic Neuron ,medicine.drug ,Human ,Signal Transduction ,Diabetes mellitu ,QH301-705.5 ,Catalysis ,Diabetes Mellitus, Experimental ,Diabetes Complications ,Inorganic Chemistry ,Diabetes mellitus ,Animals ,Humans ,Cognitive Dysfunction ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,business.industry ,Animal ,Dopaminergic Neurons ,Organic Chemistry ,medicine.disease ,Glucose ,chemistry ,Hyperglycemia ,business ,Neuroscience - Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia, responsible for the onset of several long-term complications. Recent evidence suggests that cognitive dysfunction represents an emerging complication of DM, but the underlying molecular mechanisms are still obscure. Dopamine (DA), a neurotransmitter essentially known for its relevance in the regulation of behavior and movement, modulates cognitive function, too. Interestingly, alterations of the dopaminergic system have been observed in DM. This review aims to offer a comprehensive overview of the most relevant experimental results assessing DA’s role in cognitive function, highlighting the presence of dopaminergic dysfunction in DM and supporting a role for glucotoxicity in DM-associated dopaminergic dysfunction and cognitive impairment. Several studies confirm a role for DA in cognition both in animal models and in humans. Similarly, significant alterations of the dopaminergic system have been observed in animal models of experimental diabetes and in diabetic patients, too. Evidence is accumulating that advanced glycation end products (AGEs) and their precursor methylglyoxal (MGO) are associated with cognitive impairment and alterations of the dopaminergic system. Further research is needed to clarify the molecular mechanisms linking DM-associated dopaminergic dysfunction and cognitive impairment and to assess the deleterious impact of glucotoxicity.
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- 2021
47. Kidney Disease Management in the Hospital Setting: A Focus on Inappropriate Drug Prescriptions in Older Patients
- Author
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Vincenzo, Arcoraci, Maria Antonietta Barbieri, Michelangelo, Rottura, Alessandro, Nobili, Giuseppe, Natoli, Christiano, Argano, Giovanni, Squadrito, Francesco, Squadrito, Salvatore, Corrao, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Massimo, Raspanti, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, DE GIORGI, Alfredo, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Francesco, Salerno, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Francesco, Violi, Ludovica, Perri, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Silvia, Ghidoni, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo., Arcoraci V., Barbieri M.A., Rottura M., Nobili A., Natoli G., Argano C., Squadrito G., Squadrito F., and Corrao S.
- Subjects
medicine.medical_specialty ,appropriateness of prescription ,prescribing patterns ,Renal function ,Context (language use) ,RM1-950 ,Logistic regression ,NO ,chemistry.chemical_compound ,older patient ,Internal medicine ,hospital setting ,medicine ,Pharmacology (medical) ,LS4_4 ,Medical prescription ,prescribing pattern ,appropriateness of prescriptions, chronic kidney disease, hospital setting, older patients, prescribing patterns, real-world data ,Original Research ,Pharmacology ,Creatinine ,real-world data ,business.industry ,Retrospective cohort study ,medicine.disease ,older patients ,appropriateness of prescriptions ,chronic kidney disease ,chemistry ,Observational study ,Therapeutics. Pharmacology ,business ,Kidney disease - Abstract
Aging with multimorbidity and polytherapy are the most significant factors that could led to inappropriate prescribing of contraindicated medications in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the prescriptions of contraindicated drugs in older adults in CKD and to identify their associated factors in a hospital context. An observational retrospective study was carried out considering all patients ≥65 years with at least one serum creatinine value recorded into the REPOSI register into 2010–2016 period. The estimated glomerular filtration rate (eGFR) was applied to identify CKD. A descriptive analysis was performed to compare demographic and clinical characteristics; logistic regression models were used to estimate factors of inappropriate and percentage changes of drug use during hospitalization. A total of 4,713 hospitalized patients were recorded, of which 49.8% had an eGFR 2; the 21.9% were in treatment with at least one inappropriate drug at the time of hospital admission with a decrease of 3.0% at discharge (p = 0.010). The probability of using at least one contraindicated drug was significantly higher in patients treated with more several drugs (OR 1.21, 95% CI 1.16–1.25, p p < 0.001; G5: 19.38, 11.51–32.64, p < 0.001). Low-dose acetylsalicylic acid was the contraindicated drug mainly used at the time of admission, reducing 1.2% at discharge. An overall increase in therapeutic appropriateness in hospitalized older patients with CKD was observed, despite a small percentage of therapeutic inappropriateness at discharge that underlines the need for a closer collaboration with the pharmacologist to improve the drug management.
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- 2021
48. A different mechanism of C-type inactivation in the Kv-like KcsA mutant E71V
- Author
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João Medeiros-Silva, Ahmed Rohaim, Bram J. A. Vermeulen, Federico Napoli, Jing Li, Felix Kümmerer, Markus Weingarth, Benoît Roux, and Lydia Blachowicz
- Subjects
Molecular dynamics ,Chemistry ,Helix ,Mutant ,Biophysics ,KcsA potassium channel ,Molecule ,Bound water ,Cardiac action potential ,Glutamic acid - Abstract
A large class of K+ channels display a time-dependent phenomenon called C-type inactivation whereby prolonged activation by an external stimulus leads to a non-conductive conformation of the selectivity filter. C-type inactivation is of great physiological importance particularly in voltage-activated K+ channels (Kv), affecting the firing patterns of neurons and shaping cardiac action potentials. While understanding the molecular basis of inactivation has a direct impact on human health, its structural basis remains unresolved. Knowledge about C-type inactivation has been largely deduced from the pH-activated bacterial K+ channel KcsA, whose selectivity filter under inactivating conditions adopts a constricted conformation at the level of the central glycine (TTVGYGD) that is stabilized by tightly bound water molecules. However, C-type inactivation is highly sensitive to the molecular environment surrounding the selectivity filter in the pore domain, which is different in Kv channels than in the model KcsA. In particular, a glutamic acid residue at position 71 along the pore helix in KcsA is consistently substituted by a nonpolar valine in most Kv channels, suggesting that this side chain is an important molecular determinant of function. Here, a combination of X-ray crystallography, solid-state NMR and molecular dynamics simulations of the E71V mutant of KcsA is undertaken to explore the features associated with this Kv-like construct. In both X-ray and ssNMR data, it is observed that the filter of the Kv-like KcsA mutant does not adopt the familiar constricted conformation under inactivating conditions. Rather, the filter appears to adopt a conformation that is slightly narrowed and rigidified over its entire length. No structural inactivation water molecules are present. On the other hand, molecular dynamics simulations indicate that the familiar constricted conformation can nonetheless be stably established in the mutant channel. Together, these findings suggest that the Kv-like E71V mutation in the KcsA channel may be associated with different modes of C-type inactivation, showing that distinct selectivity filter environments entail distinct C-type inactivation mechanisms.
- Published
- 2021
49. Sulforaphane improves mitochondrial metabolism in fibroblasts from patients with fragile X-associated tremor and ataxia syndrome
- Author
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Eleonora Napoli, Randi J Hagerman, Yasmeen Mansuri, Cecilia R Giulivi, and Amanda Flores
- Subjects
0301 basic medicine ,Male ,Phytochemicals ,Disease ,Neurodegenerative ,Bioinformatics ,Antioxidants ,Unfolded protein response ,chemistry.chemical_compound ,0302 clinical medicine ,Isothiocyanates ,Tremor ,80 and over ,2.1 Biological and endogenous factors ,Aetiology ,Aged, 80 and over ,Pediatric ,Neurodegeneration ,Brain ,Middle Aged ,Mitochondria ,Neurology ,Sulfoxides ,Neurological ,Female ,medicine.symptom ,RC321-571 ,Proteasome Endopeptidase Complex ,Ataxia ,Neuromuscular disease ,NF-E2-Related Factor 2 ,Iron ,Intellectual and Developmental Disabilities (IDD) ,Clinical Sciences ,Neurosciences. Biological psychiatry. Neuropsychiatry ,In Vitro Techniques ,Bioenergetics ,Article ,NRF2 ,03 medical and health sciences ,Rare Diseases ,Clinical Research ,Triplet nucleotide repeat diseases ,Complementary and Integrative Health ,medicine ,Genetics ,Humans ,Risk factor ,Aged ,Nutrition ,Neurology & Neurosurgery ,business.industry ,Neurosciences ,Fibroblasts ,medicine.disease ,FMR1 ,Brain Disorders ,Oxidative Stress ,030104 developmental biology ,Good Health and Well Being ,chemistry ,Fragile X Syndrome ,Unfolded Protein Response ,business ,Energy Metabolism ,030217 neurology & neurosurgery ,Sulforaphane - Abstract
CGG expansions between 55 and 200 in the 5'-untranslated region of the fragile-X mental retardation gene (FMR1) increase the risk of developing the late-onset debilitating neuromuscular disease Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). While the science behind this mutation, as a paradigm for RNA-mediated nucleotide triplet repeat expansion diseases, has progressed rapidly, no treatment has proven effective at delaying the onset or decreasing morbidity, especially at later stages of the disease. Here, we demonstrated the beneficial effect of the phytochemical sulforaphane (SFN), exerted through NRF2-dependent and independent manner, on pathways relevant to brain function, bioenergetics, unfolded protein response, proteosome, antioxidant defenses, and iron metabolism in fibroblasts from FXTAS-affected subjects at all disease stages. This study paves the way for future clinical studies with SFN in the treatment of FXTAS, substantiated by the established use of this agent in clinical trials of diseases with NRF2 dysregulation and in which age is the leading risk factor.
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- 2021
50. Brain Atrophy and White Matter Damage Linked to Peripheral Bioenergetic Deficits in the Neurodegenerative Disease FXTAS
- Author
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Cecilia R Giulivi, Jun Yi Wang, Eleonora Napoli, Kyoungmi Kim, Randi J Hagerman, and Yingratana A. McLennan
- Subjects
Male ,cognition ,Aging ,Neurodegenerative ,Mitochondrion ,bioenergetics ,Monocytes ,Fragile X Mental Retardation Protein ,Adenosine Triphosphate ,Tremor ,2.1 Biological and endogenous factors ,Biology (General) ,Aetiology ,FMR1 ,Cells, Cultured ,Spectroscopy ,Pediatric ,screening and diagnosis ,Cultured ,medicine.diagnostic_test ,General Medicine ,Middle Aged ,white matter hyperintensities ,White Matter ,Mitochondria ,Computer Science Applications ,mitochondria ,Chemistry ,Detection ,medicine.anatomical_structure ,peripheral blood monocytic cells ,Neurological ,Brain size ,Flavin-Adenine Dinucleotide ,Biomedical Imaging ,Female ,medicine.symptom ,MRI ,Adult ,medicine.medical_specialty ,Ataxia ,QH301-705.5 ,Cells ,Intellectual and Developmental Disabilities (IDD) ,brain ,Clinical Trials and Supportive Activities ,Article ,Catalysis ,Inorganic Chemistry ,White matter ,Rare Diseases ,Atrophy ,Clinical Research ,Internal medicine ,Genetics ,medicine ,Humans ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Aged ,volume ,Chemical Physics ,business.industry ,Organic Chemistry ,aging ,Neurosciences ,Magnetic resonance imaging ,medicine.disease ,Hyperintensity ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,Endocrinology ,Fragile X Syndrome ,Other Biological Sciences ,Energy Metabolism ,Other Chemical Sciences ,business - Abstract
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder affecting subjects (premutation carriers) with a 55-200 CGG-trinucleotide expansion in the 5′UTR of the fragile X mental retardation 1 gene (FMR1) typically after age 50. As both the presence of white matter hyperintensities (WMHs) and atrophied gray matter on magnetic resonance imaging (MRI) are linked to age-dependent decline in cognition, here we tested whether MRI outcomes (WMH volume (WMHV) and brain volume) were correlated with mitochondrial bioenergetics from peripheral blood monocytic cells in 87 carriers with and without FXTAS. As a parameter assessing cumulative damage, WMHV was correlated to both FXTAS stages and age, and brain volume discriminated between carriers and non-carriers. Similarly, mitochondrial mass and ATP production showed an age-dependent decline across all participants, but in contrast to WMHV, only FADH2-linked ATP production was significantly reduced in carriers vs. non-carriers. In carriers, WMHV negatively correlated with ATP production sustained by glucose-glutamine and FADH2-linked substrates, whereas brain volume was positively associated with the latter and mitochondrial mass. The observed correlations between peripheral mitochondrial bioenergetics and MRI findings—and the lack of correlations with FXTAS diagnosis/stages—may stem from early brain bioenergetic deficits even before overt FXTAS symptoms and/or imaging findings.
- Published
- 2021
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