94 results on '"Guiotto A"'
Search Results
2. Deregulated NLRP3 inflammasome response due to a constitutive activation of NF-κB p65 pro-inflammatory pathway in lymphomonocytes of Rett syndrome patients
- Author
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Valeria Cordone, Andrea Vallese, Alessandra Pecorelli, Anna Guiotto, Francesca Ferrara, Mascia Benedusi, Franco Cervellati, Joussef Hayek, and Giuseppe Valacchi
- Subjects
Physiology (medical) ,Biochemistry - Published
- 2023
3. Constitutive activation of NLRP3 inflammasome machinery in ex-vivo models of Rett syndrome: from pathogenetic role to new potential therapeutic target
- Author
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Valeria Cordone, Alessandra Pecorelli, Francesca Ferrara, Anna Guiotto, Joussef Hayek, Carlo Cervellati, Fernanda Amicarelli, and Giuseppe Valacchi
- Subjects
Physiology (medical) ,Biochemistry - Published
- 2023
4. Loss of Scavenger Receptor B1 (SR-B1) in Brain of a Rett Syndrome Mouse Model
- Author
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Alessandra Pecorelli, Francesca Ferrara, Anna Guiotto, Andrea Vallese, Valeria Cordone, Giuseppe Belmonte, Joussef Hayek, Carlo Cervellati, and Giuseppe Valacchi
- Subjects
Physiology (medical) ,Biochemistry - Published
- 2022
5. The role of potassium current in the pulmonary response to environmental oxidative stress
- Author
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Rita Canella, Mascia Benedusi, Andrea Vallese, Alessandra Pecorelli, Anna Guiotto, Francesca Ferrara, Giorgio Rispoli, Franco Cervellati, and Giuseppe Valacchi
- Subjects
Biophysics ,Molecular Biology ,Biochemistry - Published
- 2023
6. Circadian Clock and OxInflammation: Functional Crosstalk in Cutaneous Homeostasis
- Author
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Mascia Benedusi, Anna Guiotto, Elena Frigato, Cristiano Bertolucci, and Giuseppe Valacchi
- Subjects
Keratinocytes ,skin ,Aging ,Article Subject ,Circadian clock ,Cellular homeostasis ,Inflammation ,Biology ,Biochemistry ,NRF2 ,Shift work ,Economica ,Circadian Clocks ,medicine ,Homeostasis ,Humans ,oxidative stress ,pollution ,Circadian rhythm ,Transcription factor ,Cells, Cultured ,induced damage ,QH573-671 ,NF-kappa B ,Cell Biology ,General Medicine ,Crosstalk (biology) ,NRF2, NF-kappa B, oxidative stress, induced damage, skin, pollution ,medicine.symptom ,Cytology ,Neuroscience ,Research Article - Abstract
Circadian rhythms are biological oscillations that occur with an approximately 24 h period and optimize cellular homeostasis and responses to environmental stimuli. A growing collection of data suggests that chronic circadian disruption caused by novel lifestyle risk factors such as shift work, travel across time zones, or irregular sleep-wake cycles has long-term consequences for human health. Among the multiplicity of physiological systems hypothesized to have a role in the onset of pathologies in case of circadian disruption, there are redox-sensitive defensive pathways and inflammatory machinery. Due to its location and barrier physiological role, the skin is a prototypical tissue to study the influence of environmental insults induced OxInflammation disturbance and circadian system alteration. To better investigate the link among outdoor stressors, OxInflammation, and circadian system, we tested the differential responses of keratinocytes clock synchronized or desynchronized, in an in vitro inflammatory model exposed to O3. Being both NRF2 and NF-κB two key redox-sensitive transcription factors involved in cellular redox homeostasis and inflammation, we analyzed their activation and expression in challenged keratinocytes by O3. Our results suggest that a synchronized circadian clock not only facilitates the protective role of NRF2 in terms of a faster and more efficient defensive response against environmental insults but also moderates the cellular damage resulting from a condition of chronic inflammation. Our results bring new insights on the role of circadian clock in regulating the redox-inflammatory crosstalk influenced by O3 and possibly can be extrapolated to other pollutants able to affect the oxinflammatory cellular processes.
- Published
- 2020
7. The constitutive activation of TLR4-IRAK1- NFκB axis is involved in the early NLRP3 inflammasome response in peripheral blood mononuclear cells of Rett syndrome patients
- Author
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Valeria Cordone, Francesca Ferrara, Alessandra Pecorelli, Anna Guiotto, Antonio Vitale, Fernanda Amicarelli, Carlo Cervellati, Joussef Hayek, and Giuseppe Valacchi
- Subjects
p65 ,Inflammasomes ,Interleukin-1beta ,Interleukin-18 ,NF-kappa B ,Oxinflammation ,Biochemistry ,Interleukin-1β ,NO ,Toll-Like Receptor 4 ,Interleukin-1 Receptor-Associated Kinases ,Physiology (medical) ,NLR Family, Pyrin Domain-Containing 3 Protein ,Leukocytes, Mononuclear ,Rett Syndrome ,Humans ,MeCP2 - Abstract
Rett syndrome (RTT), a devastating neurodevelopmental disorder, is caused in 95% of the cases by mutations in the X-chromosome-localized MECP2 gene. To date, RTT is considered a broad-spectrum disease, due to multisystem disturbances affecting patients, associated with mitochondrial dysfunctions, subclinical inflammation and an overall OxInflammatory status. Inflammasomes are multi-protein complexes crucially involved in innate immune responses against pathogens and oxidative stress mediators. The assembly of NLRP3:ASC inflammasome lead to pro-caspase 1 activation, maturation of interleukins (IL)-1β and 18 and proteolytic cleavage of Gasdermin D leading eventually to pyroptosis and systemic inflammation. The possible de-regulation of this system, in parallel with upstream nuclear factor (NF)-κB p65 pathway, were analyzed in peripheral blood mononuclear cells (PBMCs) and plasma isolated from RTT patients and matching controls. RTT PBMCs showed a constitutive activation of the axis TLR4 (Toll-like receptor 4)-IRAK1 (interleukin-1 receptor associated kinase 1)-NF-κB p65, together with augmented ROS generation and enhanced IL-18 mRNA levels and NLRP3:ASC co-localization. The deregulation of inflammasome components was even found in THP-1 cells silenced for MECP2 and importantly, in plasma compartment of RTT subjects, from the earliest stages of the pathology or in correlation with the severity of MeCP2 mutations. Taken together, these data provide new insights into the mechanisms involved in RTT sub-clinical inflammatory status present in RTT patients, thus helping to reveal new targets for future therapeutic approaches.
- Published
- 2022
8. Bacterial ligands as flexible and sensitive detectors in rapid tests for antibodies to SARS-CoV-2
- Author
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Simone Cavalera, Fabio Di Nardo, Matteo Chiarello, Thea Serra, Barbara Colitti, Cristina Guiotto, Franca Fagioli, Celeste Cagnazzo, Marco Denina, Annagloria Palazzo, Fiora Artusio, Roberto Pisano, Sergio Rosati, Claudio Baggiani, and Laura Anfossi
- Subjects
Immunoassay ,Serological testing ,Design of experiment ,Broad-specific ligands ,Gold nanoparticles ,Lateral flow immunoassay ,SARS-CoV-2 ,COVID-19 ,Metal Nanoparticles ,Antibodies, Viral ,Biochemistry ,Sensitivity and Specificity ,Analytical Chemistry ,Dogs ,Cats ,Animals ,Gold - Abstract
Lateral flow immunoassay (LFIA) is widely employed as point-of-care tests (POCT) for the diagnosis of infectious diseases. The accuracy of LFIA largely depends on the quality of the immunoreagents used. Typical LFIAs to reveal the immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) employ anti-human immunoglobulin (hIG) antibodies and recombinant viral antigens, which usually are unstable and poorly soluble. Broad selective bacterial proteins, such as Staphylococcal protein A (SpA) and Streptococcal protein G (SpG) can be considered alternatives to anti-hIG to increase versatility and sensitivity of serological LFIAs because of their high binding capacity, interspecies reactivity, and robustness. We developed two colorimetric LFA devices including SpA and SpG linked to gold nanoparticles (GNP) as detectors and explored the use of a specific, stable, and soluble immunodominant fraction of the nucleocapsid protein from SARS-CoV-2 as the capturing agent. The optimal amount of SpA-GNP and SpG-GNP conjugates and the protein-to-GNP ratios were defined through a full factorial experimental design to maximize the diagnostic sensitivity of the LFIAs. The new LFA devices were applied to analyze 105 human serum samples (69 positive and 36 negatives according to reference molecular diagnostic methods). The results showed higher sensitivity (89.9%, 95% CI 82.7–97.0) and selectivity (91.7%, 82.6–100) for the SpA-based compared to the SpG-based LFA. In addition, 18 serum samples from cats and dogs living with COVID-19 patients were analyzed and 14 showed detectable levels of anti-SARS-CoV-2 antibodies, thus illustrating the flexibility of the SpA- and SpG-based LFAs.Graphical abstract
- Published
- 2022
9. Ubiquitination as a key regulatory mechanism for O3-induced cutaneous redox Inflammasome activation
- Author
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Francesca Ferrara, Valeria Cordone, Alessandra Pecorelli, Mascia Benedusi, Erika Pambianchi, Anna Guiotto, Andrea Vallese, Franco Cervellati, and Giuseppe Valacchi
- Subjects
Physiology (medical) ,Organic Chemistry ,Clinical Biochemistry ,Biochemistry - Published
- 2022
10. Involvement Of Ferroptosis In Rett Syndrome
- Author
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Anna Guiotto, Valeria Cordone, Mascia Benedusi, Franco CERVELLATI, Carlo Cervellati, Joussef Hayek, Giuseppe Valacchi, and Alessandra Pecorelli
- Subjects
Physiology (medical) ,Biochemistry - Published
- 2022
11. A possible role for the loss of brain Scavenger Receptor B1 (SR-B1) in Rett syndrome
- Author
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Alessandra Pecorelli, Valeria Cordone, Anna Guiotto, Joussef Hayek, Carlo Cervellati, and Giuseppe Valacchi
- Subjects
Physiology (medical) ,Biochemistry - Published
- 2022
12. [YIA] Evidence of ferroptosis involvement in Rett syndrome pathogenesis
- Author
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Anna Guiotto, Valeria Cordone, Andrea Vallese, Mascia Benedusi, Franco Cervellati, Joussef Hayek, Carlo Cervellati, Giuseppe Valacchi, and Alessandra Pecorelli
- Subjects
Physiology (medical) ,Biochemistry - Published
- 2022
13. Feasibility and Reliability Assessment of Video-Based Motion Analysis and Surface Electromyography in Children with Fragile X during Gait
- Author
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Weronika Joanna Piątkowska, Roberta Polli, Annamaria Guiotto, Fabiola Spolaor, A. Ciniglio, Marco Ricca, F. Cibin, Zimi Sawacha, and Alessandra Murgia
- Subjects
Range of Motion ,030506 rehabilitation ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Electromyography ,TP1-1185 ,surface electromyography ,Biochemistry ,Biceps ,Article ,Analytical Chemistry ,Fragile X syndrome ,Gait analysis ,Kinematics ,Surface electromyography ,Biomechanical Phenomena ,Child ,Feasibility Studies ,Humans ,Range of Motion, Articular ,Reproducibility of Results ,Gait ,Muscle, Skeletal ,03 medical and health sciences ,0302 clinical medicine ,Gait (human) ,Physical medicine and rehabilitation ,medicine ,Electrical and Electronic Engineering ,fragile X syndrome ,Instrumentation ,medicine.diagnostic_test ,business.industry ,Chemical technology ,Motor control ,Skeletal ,medicine.disease ,Atomic and Molecular Physics, and Optics ,medicine.anatomical_structure ,kinematics ,gait analysis ,Autism ,Muscle ,Ankle ,0305 other medical science ,business ,030217 neurology & neurosurgery ,Articular - Abstract
Fragile X Syndrome (FXS), the leading form of inherited intellectual disability and autism, is characterized by specific musculoskeletal conditions. We hypothesized that gait analysis in FXS could be relevant for the evaluation of motor control of gait, and help the understanding of a possible correlation between functional and intellectual abilities. Typical deficits in executive control and hyperactivity have hampered the use of standard gait analysis. The aim of our study was to quantitatively assess musculoskeletal alterations in FXS children in standard ambulatory conditions, in a friendly environment. Ten FXS children and sixteen controls, with typical neurodevelopment, were evaluated through four synchronized video cameras and surface electromyography, lower limb joints rotations, spatiotemporal parameters, duration of muscle contraction, activation timing and envelope peaks were determined. Reliability and repeatability of the video based kinematics analysis was assessed with respect to stereophotogrammetry. The Kruskal–Wallis Test (p <, 0.05) or SPM1D were used to compare different groups of subjects. Results show a consistently altered gait pattern associated with abnormal muscle activity in FXS subjects: reduced knee and excessive hip and ankle flexion, and altered duration and activity onset on all the recorded muscles (Rectus/Biceps Femoris, Tibialis Anterior, Gastrocnemius Lateralis). Results of this study could help with planning personalized rehabilitations.
- Published
- 2021
14. Mitochondrial dynamics and quality control pathways impairment in Rett Syndrome and Autism Spectrum Disorder
- Author
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Alessandra Pecorelli, Anna Guiotto, Valeria Cordone, Franco Cervellati, Mascia Benedusi, Carlo Cervellati, Joussef Hayek, and Giuseppe Valacchi
- Subjects
Physiology (medical) ,Biochemistry - Published
- 2021
15. The Design and Simulation of a 16-Sensors Plantar Pressure Insole Layout for Different Applications: From Sports to Clinics, a Pilot Study
- Author
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Fabiola Spolaor, Zimi Sawacha, Annamaria Guiotto, and A. Ciniglio
- Subjects
Adult ,layout ,Mean squared error ,weight lifting ,0206 medical engineering ,Pilot Projects ,Walking ,02 engineering and technology ,Drop landing ,Gait analysis ,Layout ,Plantar pressure insoles ,Weight lifting ,lcsh:Chemical technology ,Biochemistry ,Article ,drop landing ,Analytical Chemistry ,Wearable Electronic Devices ,03 medical and health sciences ,0302 clinical medicine ,Gait (human) ,Germany ,Pressure ,Humans ,lcsh:TP1-1185 ,Electrical and Electronic Engineering ,Ground reaction force ,Gait ,Instrumentation ,Simulation ,Mathematics ,Forefoot ,Plantar pressure ,030229 sport sciences ,020601 biomedical engineering ,Atomic and Molecular Physics, and Optics ,Biomechanical Phenomena ,Shoes ,gait analysis ,plantar pressure insoles ,Center of pressure (fluid mechanics) - Abstract
The quantification of plantar pressure distribution is widely done in the diagnosis of lower limbs deformities, gait analysis, footwear design, and sport applications. To date, a number of pressure insole layouts have been proposed, with different configurations according to their applications. The goal of this study is to assess the validity of a 16-sensors (1.5 × 1.5 cm) pressure insole to detect plantar pressure distribution during different tasks in the clinic and sport domains. The data of 39 healthy adults, acquired with a Pedar-X® system (Novel GmbH, Munich, Germany) during walking, weight lifting, and drop landing, were used to simulate the insole. The sensors were distributed by considering the location of the peak pressure on all trials: 4 on the hindfoot, 3 on the midfoot, and 9 on the forefoot. The following variables were computed with both systems and compared by estimating the Root Mean Square Error (RMSE): Peak/Mean Pressure, Ground Reaction Force (GRF), Center of Pressure (COP), the distance between COP and the origin, the Contact Area. The lowest (0.61%) and highest (82.4%) RMSE values were detected during gait on the medial-lateral COP and the GRF, respectively. This approach could be used for testing different layouts on various applications prior to production.
- Published
- 2021
16. Relationship between Muscular Activity and Postural Control Changes after Proprioceptive Focal Stimulation (Equistasi®) in Middle-Moderate Parkinson’s Disease Patients: An Explorative Study
- Author
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Leila Bakdounes, Zimi Sawacha, M. Romanato, Antonella Peppe, Guiotto Annamaria, Daniele Volpe, Duc Khanh To, and Fabiola Spolaor
- Subjects
030506 rehabilitation ,medicine.medical_specialty ,Parkinson's disease ,parkinson’s disease ,surface electromyography ,Somatosensory system ,lcsh:Chemical technology ,Biochemistry ,Biceps ,Analytical Chemistry ,parkinson’s disease, neurorehabilitation device, wearable focal mechanical vibrations device, surface electromyography, balance assessment, gait analysis ,neurorehabilitation device ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,medicine ,Force platform ,lcsh:TP1-1185 ,balance assessment ,Electrical and Electronic Engineering ,Instrumentation ,Neurorehabilitation ,Vestibular system ,Proprioception ,business.industry ,medicine.disease ,Atomic and Molecular Physics, and Optics ,Gait analysis ,wearable focal mechanical vibrations device ,gait analysis ,0305 other medical science ,business ,030217 neurology & neurosurgery - Abstract
The aim of this study was to investigate the effects of Equistasi®, a wearable device, on the relationship between muscular activity and postural control changes in a sample of 25 Parkinson&rsquo, s disease (PD) subjects. Gait analysis was carried out through a six-cameras stereophotogrammetric system synchronized with two force plates, an eight-channel surface electromyographic system, recording the activity of four muscles bilaterally: Rectus femoris, tibialis anterior (TA), biceps femoris, and gastrocnemius lateralis (GL). The peak of the envelope (PoE) and its occurrence within the gait cycle (position of the peak of the envelope, PPoE) were calculated. Frequency-domain posturographic parameters were extracted while standing still on a force plate in eyes open and closed conditions for 60 s. After the treatment with Equistasi®, the mid-low (0.5&ndash, 0.75) Hz and mid-high (0.75&ndash, 1 Hz) components associated with the vestibular and somatosensory systems, PoE and PPoE, displayed a shift toward the values registered on the controls. Furthermore, a correlation was found between changes in proprioception (power spectrum frequencies during the Romberg Test) and the activity of GL, BF (PoE), and TA (PPoE). Results of this study could provide a quantitative estimation of the effects of a neurorehabilitation device on the peripheral and central nervous system in PD.
- Published
- 2021
17. Aberrant Mitochondrial Bioenergetics Fuels Inflammasome Machinery in Autism Spectrum Disorder
- Author
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Alessandra Pecorelli, Ferrara Francesca, Valeria Cordone, Anna Guiotto, Carlo Cervellati, Joussef Hayek, and Giuseppe Valacchi
- Subjects
Physiology (medical) ,Biochemistry - Published
- 2022
18. Effects of rapid palatal expansion on chewing biomechanics in children with malocclusion: A surface electromyography study
- Author
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Fabiola Spolaor, Giovanni Bruno, Antonio Gracco, Martina Mason, Zimi Sawacha, Ottavia Surace, Annamaria Guiotto, and Alberto De Stefani
- Subjects
Male ,Palatal Expansion Technique ,Temporal Muscle ,Electromyography ,Posterior crossbite ,lcsh:Chemical technology ,Biochemistry ,Article ,Analytical Chemistry ,Rapid palatal expansion ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,lcsh:TP1-1185 ,Electrical and Electronic Engineering ,Child ,Instrumentation ,Children ,Orthodontics ,medicine.diagnostic_test ,Crossbite ,business.industry ,Masseter Muscle ,Biomechanics ,Healthy subjects ,030206 dentistry ,medicine.disease ,Atomic and Molecular Physics, and Optics ,Masticatory force ,Temporomandibular joint ,medicine.anatomical_structure ,Female ,Malocclusion ,business ,030217 neurology & neurosurgery - Abstract
Malocclusion during childhood may affect both morphology and masticatory function and could greatly affect the subsequent growth and development of the jaws and face. The purpose of this study was to evaluate the efficiency of surface electromyography in describing the effects of the rapid palatal expansion (RPE) on Masseter (M) and Temporalis Anterior (T) muscles&rsquo, activity in 53 children with different types of malocclusion: bilateral posterior crossbite (BPcb), underdeveloped maxillary complex without crossbite (NOcb) and unilateral posterior crossbite on the right (UPCBr) and on the left (UPCBl). The muscular activities during chewing tasks were assessed bilaterally before and after RPE application and three months after removal. Both the envelope&rsquo, s peak (µ, V) and its occurrence (% of chewing task) were extracted from the surface electromyography signal. Our results showed the presence of statistically significant differences (p <, 0.05) on temporomandibular joint muscles, across different assessments, in all the tested populations of subjects. Surface electromyography demonstrated a relationship between the correction of a maxillary transverse discrepancy and the restoration of a muscle&rsquo, s activation patterns comparable to healthy subjects for both T and M.
- Published
- 2020
19. Reliability and Repeatability of ACL Quick Check®: A Methodology for on Field Lower Limb Joint Kinematics and Kinetics Assessment in Sport Applications
- Author
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Annamaria Guiotto, Alfredo Ciniglio, Fabiola Spolaor, Davide Pavan, Federica Cibin, Alex Scaldaferro, and Zimi Sawacha
- Subjects
ACL injury ,Knee Joint ,Anterior Cruciate Ligament Injuries ,Chemical technology ,joint moments ,video analysis ,plantar pressure ,sagittal plane kinematics of squat ,Reproducibility of Results ,TP1-1185 ,Biochemistry ,Atomic and Molecular Physics, and Optics ,Biomechanical Phenomena ,Analytical Chemistry ,body regions ,Kinetics ,Lower Extremity ,Humans ,Anterior Cruciate Ligament ,Electrical and Electronic Engineering ,human activities ,Instrumentation ,Joint moments ,Plantar pressure ,Sagittal plane kinematics of squat ,Video analysis - Abstract
Anterior cruciate ligament (ACL) lesion represents one of the most dramatic sport injuries. Even though clinical screenings aiming at identifying subjects at risk of injuries are gaining popularity, the use of sophisticated equipment still represents a barrier towards their widespread use. This study aimed to test both reliability and repeatability of a new methodology to assess lower limb joints kinematics and kinetics directly on field with the aid of video cameras and plantar pressure insoles. Ten athletes and one case study (post ACL surgery) were assessed in a gait laboratory, while performing double leg squats, through the simultaneous acquisition of stereophotogrammetry, force plates, commercial video cameras and plantar pressure insoles. Different sources of errors were investigated and both reliability and repeatability analysis performed. Minimum and maximum RMSE values of 0.74% (right knee joint center trajectory) and 64.51%, respectively (ankle dorsi-plantarflexion moment), were detected. Excellent to good correlation was found for the majority of the measures, even though very poor and inverse between-trials correlation was found on a restricted number of trials especially for the ankle dorsi-plantarflexion moment. These findings could be used in combination with already available screening tools in order to provide more repeatable results.
- Published
- 2021
20. Improper enzymatic defensive responses in Rett syndrome disorder
- Author
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Anna Guiotto, Valeria Cordone, Mascia Benedusi, Franco Cervellati, Joussef Hayek, Carlo Cervellati, Giuseppe Valacchi, and Alessandra Pecorelli
- Subjects
Physiology (medical) ,Biochemistry - Published
- 2021
21. Ubiquitination as a key regulatory mechanism for O3-induced cutaneous redox inflammasome activation
- Author
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Anna Guiotto, Mascia Benedusi, Giuseppe Valacchi, Erika Pambianchi, Francesca Ferrara, Alessandra Pecorelli, and Franco Cervellati
- Subjects
Ubiquitin ,biology ,Chemistry ,Mechanism (biology) ,Physiology (medical) ,Key (cryptography) ,biology.protein ,medicine ,Inflammasome ,Biochemistry ,Redox ,medicine.drug ,Cell biology - Published
- 2021
22. NALP1 involvement in cigarette smoke induces cutaneous inflammation
- Author
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Giuseppe Valacchi, Mascia Benedusi, Anna Guiotto, Franco Cervellati, Francesca Ferrara, and Roxane Prieux
- Subjects
business.industry ,Physiology (medical) ,Immunology ,Cigarette smoke ,Medicine ,Cutaneous inflammation ,business ,Biochemistry - Published
- 2021
23. Evaluation of 99th percentile and reference change values of a high-sensitivity cTnI method: A multicenter study
- Author
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Tommaso Fasano, Silvia Masotti, Cinzia Carrozza, Simona Storti, Simone Canovi, Aldo Clerico, Mario Correale, Andrea Ripoli, Lucia Belloni, Cristina Guiotto, Sara Rizzardi, Ruggero Dittadi, Mariella Dipalo, Veronica Musetti, Domenico Cosseddu, Marco Alfonso Perrone, Marco Migliardi, Concetta Prontera, Sergio Bernardini, and Rosalia Aloe
- Subjects
0301 basic medicine ,Male ,limit of quantitation ,very elderly ,Clinical Biochemistry ,electrolyte ,Biochemistry ,young adult, Adolescent ,human experiment ,Cohort Studies ,chemistry.chemical_compound ,Electrocardiography ,0302 clinical medicine ,Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,sensitivity analysis ,Reference Values ,Acute coronary syndrome ,Cardiac troponins ,High-sensitivity methods ,Myocardial infarction ,Reference population ,Risk stratification ,Adolescent ,Adult ,Aged ,Aged, 80 and over ,Cardiac-Gated Imaging Techniques ,Female ,Healthy Volunteers ,Humans ,Italy ,Middle Aged ,Troponin I ,Troponin T ,Young Adult ,80 and over ,glucose ,cardiac gated imaging ,limit of detection ,Settore BIO/12 ,creatinine ,clinical trial ,General Medicine ,cohort analysis ,limit of blank ,priority journal ,030220 oncology & carcinogenesis ,laboratory test ,Cohort ,standards ,blood sampling ,medicine.symptom ,medicine.medical_specialty ,sex difference ,troponin T, adult ,volunteer ,Asymptomatic ,Article ,cardiac imaging ,03 medical and health sciences ,99th percentile ,blood ,Internal medicine ,medicine ,human ,normal human ,Creatinine ,normal value ,business.industry ,practice guideline ,Biochemistry (medical) ,reference value ,medicine.disease ,030104 developmental biology ,multicenter study ,Multicenter study ,chemistry ,age ,blood cell count ,business - Abstract
Background The Italian Society of Clinical Biochemistry (SIBioC) and the Italian Section of the European Ligand Assay Society (ELAS) have recently promoted a multicenter study (Italian hs-cTnI Study) with the aim to accurately evaluate analytical performances and reference values of the most popular cTnI methods commercially available in Italy. The aim of this article is to report the results of the Italian hs-cTnI Study concerning the evaluation of the 99th percentile URL and reference change (RCV) values around the 99th URL of the Access cTnI method. Materials and methods Heparinized plasma samples were collected from 1306 healthy adult volunteers by 8 Italian clinical centers. Every center collected from 50 to 150 plasma samples from healthy adult subjects. All volunteers denied the presence of chronic or acute diseases and had normal values of routine laboratory tests (including creatinine, electrolytes, glucose and blood counts). An older cohort of 457 adult subjects (mean age 63.0 years; SD 8.1 years, minimum 47 years, maximum 86 years) underwent also ECG and cardiac imaging analysis in order to exclude the presence of asymptomatic cardiac disease. Results and conclusions The results of the present study confirm that the Access hsTnI method using the DxI platform satisfies the two criteria required by international guidelines for high-sensitivity methods for cTn assay. Furthermore, the results of this study confirm that the calculation of the 99th percentile URL values are greatly affected not only by age and sex of the reference population, but also by the statistical approach used for calculation of cTnI distribution parameters.
- Published
- 2019
24. Evaluation of 99th percentile value of a chemiluminescence enzyme immunoassay (CLEIA) for cTnI using the automated AIA-CL2400 platform
- Author
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Aldo Clerico, Silvia Masotti, Tommaso Fasano, Veronica Musetti, Sara Rizzardi, Ruggero Dittadi, Cristina Guiotto, Marco Alfonso Perrone, Concetta Prontera, Antonio de Santis, Cinzia Carrozza, and Rosalia Aloe
- Subjects
Male ,Letter ,limit of quantitation ,Clinical Biochemistry ,reference value, Automation ,Biochemistry ,law.invention ,Immunoenzyme Techniques ,Automation ,Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,law ,Reference Values ,middle aged ,Reference population ,High-sensitivity methods ,limit of detection ,medicine.diagnostic_test ,adult ,Myocardium metabolism ,General Medicine ,chemiluminescence enzyme immunoassay ,enzyme immunoassay ,aged ,chemiluminescence immunoassay ,female ,Italy ,priority journal ,Acute coronary syndrome ,devices ,Cardiac troponin ,cardiac muscle ,99th percentile ,medicine ,troponin I ,luminescence ,Humans ,controlled study ,human ,intermethod comparison ,Chemiluminescence ,Chromatography ,business.industry ,Myocardium ,Biochemistry (medical) ,reference value ,calibration ,troponin I, adult ,Myocardial infarction ,Immunoassay ,Reference values ,Luminescent Measurements ,Cardiac troponins ,business ,metabolism - Published
- 2019
25. Microgravity induces cellular senescence in human keratinocytes
- Author
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Mascia Benedusi, Anna Guiotto, Rita Canella, Franco Cervellati, Giuseppe Valacchi, and Francesca Ferrara
- Subjects
Physiology (medical) ,Cellular senescence ,Biology ,Biochemistry ,Cell biology - Published
- 2021
26. Aberrant NF-κB / Nrf2 cross-talk in Rett syndrome
- Author
-
Joussef Hayek, Valeria Cordone, Mascia Benedusi, Alessandra Pecorelli, Anna Guiotto, Fernanda Amicarelli, Carlo Cervellati, and Giuseppe Valacchi
- Subjects
chemistry.chemical_compound ,chemistry ,business.industry ,Physiology (medical) ,Cancer research ,Medicine ,Rett syndrome ,NF-κB ,business ,medicine.disease ,Biochemistry - Published
- 2021
27. Mitochondrial dysfunction fuels inflammasome machinery in Autism Spectrum Disorder
- Author
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Mascia Benedusi, Alessandra Pecorelli, Valeria Cordone, Anna Guiotto, Franco Cervellati, Giuseppe Valacchi, Carlo Cervellati, and Joussef Hayek
- Subjects
Autism spectrum disorder ,business.industry ,Physiology (medical) ,medicine ,Inflammasome ,medicine.disease ,business ,Biochemistry ,Neuroscience ,medicine.drug - Published
- 2021
28. Alteration of cellular defensive response and a possible involvement of ferroptosis cell death in Rett syndrome disorder
- Author
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Anna Guiotto, Mascia Benedusi, Alessandra Pecorelli, Valeria Cordone, Carlo Cervellati, Giuseppe Valacchi, Franco Cervellati, and Joussef Hayek
- Subjects
Programmed cell death ,business.industry ,Physiology (medical) ,Ferroptosis ,medicine ,Cancer research ,Rett syndrome ,medicine.disease ,business ,Biochemistry - Published
- 2021
29. Psoralenquinones as a Novel Class of Proteasome Inhibitors: Design, Synthesis and Biological Evaluation
- Author
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Adriano Guiotto, Adriana Chilin, Christine Marzano, Valentina Gandin, and Giovanni Marzaro
- Subjects
Models, Molecular ,cytotoxicity ,molecular docking ,proteasome activity ,psoralenquinones ,Antineoplastic Agents ,Computational biology ,Biochemistry ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,Humans ,Enzyme Inhibitors ,General Pharmacology, Toxicology and Pharmaceutics ,Cytotoxicity ,Biological evaluation ,Pharmacology ,Chemistry ,Organic Chemistry ,Ficusin ,Quinones ,Class (biology) ,Proteasome activity ,Design synthesis ,Proteasome ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Proteasome Inhibitors ,Protein Binding - Published
- 2011
30. Benzoquinazoline derivatives as new agents affecting DNA processing
- Author
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Antonio Toninello, Adriano Guiotto, Giovanni Marzaro, Adriana Chilin, and Lisa Dalla Via
- Subjects
Amsacrine ,Male ,Models, Molecular ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,Biochemistry ,Antitumor agents ,Benzoquinazoline ,Topoisomerase ,DNA ,HeLa ,chemistry.chemical_compound ,Salmon ,Drug Discovery ,Side chain ,Quinazoline ,Animals ,Humans ,Topoisomerase II Inhibitors ,Molecular Biology ,Cell Proliferation ,biology ,Cell growth ,Cell Cycle ,Organic Chemistry ,Biological activity ,biology.organism_classification ,chemistry ,Quinazolines ,biology.protein ,Molecular Medicine ,Topoisomerase I Inhibitors ,HeLa Cells - Abstract
A new series of benzo[h]quinazoline and benzo[f]quinazoline derivatives was prepared and studied for the biological activity. The compounds carrying a dimethylaminoethyl side chain (6c, 8c and 12) inhibit cell growth. The ability to form a molecular complex with DNA and to interfere with topoII and topoI relaxation activity was evidenced for the most active 6c and 8c, along with the capacity to induce apoptosis on HeLa cells.
- Published
- 2011
31. N-Acetylcarnosine Lubricant Eyedrops Possess All-In-One Universal Antioxidant Protective Effects of L-Carnosine in Aqueous and Lipid Membrane Environments, Aldehyde Scavenging, and Transglycation Activities Inherent to Cataracts: A Clinical Study of the New Vision-Saving Drug N-Acetylcarnosine Eyedrop Therapy in a Database Population of Over 50,500 Patients
- Author
-
Anne Kasus-Jacobi, Philip Micans, Andrea Guiotto, and Mark A. Babizhayev
- Subjects
Glycation End Products, Advanced ,Male ,Drug ,Administration, Topical ,media_common.quotation_subject ,Population ,Carnosine ,Pharmacology ,Antioxidants ,Cataract ,Lipid peroxidation ,chemistry.chemical_compound ,Double-Blind Method ,Cataracts ,Glycation ,Humans ,Medicine ,Prodrugs ,Pharmacology (medical) ,Prospective Studies ,education ,Aged ,media_common ,Aged, 80 and over ,education.field_of_study ,Cross-Over Studies ,business.industry ,General Medicine ,Middle Aged ,Macular degeneration ,medicine.disease ,Oxidative Stress ,chemistry ,Biochemistry ,Tolerability ,Delayed-Action Preparations ,Liposomes ,Female ,Lipid Peroxidation ,Ophthalmic Solutions ,business - Abstract
The antioxidant activity of L-carnosine (beta-alanyl-L-histidine, bioactivated in ocular tissues) versus N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine, ocular-targeted small dipeptide molecules) was studied in aqueous solution and in a lipid environment, employing liposomes as a model of lipid membranes. Reactive oxygen species (ROS) were generated by an iron/ascorbate promoter system for induction of lipid peroxidation (LPO). L-carnosine, which is stabilized from enzymatic hydrolysis, operates as a universal aldehyde and ROS scavenger in both aqueous and lipid environments and is effective at preventing ROS-induced damage to biomolecules. Second-generation carnosine analogs bearing the histidyl-hydrazide moiety were synthesized and tested versus L-carnosine for their ability to reverse the glycation process, also known as the Maillard reaction, and reverse the stable intermolecular cross-links, monitored in the glucose-ethylamine Schiff base model, ultimately resulting in the formation of the advanced glycation end products (AGEs) from nonenzymatic glycation, accumulating in numerous body tissues and fluids. The obtained data demonstrate the transglycation properties of the ophthalmically stabilized L-carnosine and L-carnosine histidyl-hydrazide derivatives tested and can be used to decrease or predict the occurrence of long-term complications of AGE formation and improve therapeutically the quality of vision and length of life for diabetes mellitus patients and survivors with early aging. Scientists at Innovative Vision Products, Inc. (IVP), developed lubricant eyedrops designed as a sustained-release 1% N-acetylcarnosine prodrug of L-carnosine. The eyedrops contain a mucoadhesive cellulose-based compound combined with corneal absorption promoters and glycerine in a drug-delivery system. Anti-aging therapeutics with the ophthalmic drug eyedrop formula including N-acetylcarnosine showed efficacy in the nonsurgical treatment of age-related cataracts for enrolled participants in the prospective, randomized, double-masked, placebo-controlled crossover clinical trial after controlling for age, gender, and daily activities. In a cohort in excess of 50,500 various patients seeking cutting-edge medical care, the N-acetylcarnosine topical eyedrops target therapy was demonstrated to have significant efficacy, safety, and good tolerability for the prevention and treatment of visual impairment in this older population with relatively stable patterns of causes for blindness and visual impairment. Overall, accumulated study data demonstrate that the IVP-designed new vision-saving drugs, including N-acetylcarnosine eyedrops, promote health vision and prevent vision disability from senile cataracts, primary open-angle glaucoma, age-related macular degeneration, diabetic retinopathy, and aging. N-acetylcarnosine eyedrop therapy is the crown jewel of the anti-aging medical movement and revolutionizes early detection, treatment, and rejuvenation of aging-related eye-disabling disorders. N-acetylcarnosine, as an innovative medical science tool and component of the home medicine and alternative medicine approaches, has the potential to alleviate visual impairment and its associated social, economic, and political woes for an aging population.
- Published
- 2009
32. N-Acetylcarnosine and histidyl-hydrazide are potent agents for multitargeted ophthalmic therapy of senile cataracts and diabetic ocular complications
- Author
-
Andrea Guiotto, Mark A. Babizhayev, and Anne Kasus-Jacobi
- Subjects
Male ,Drug ,Glycosylation ,media_common.quotation_subject ,Biological Availability ,Pharmaceutical Science ,Ophthalmologic Surgical Procedures ,Absorption (skin) ,Pharmacology ,Hydrazide ,Cataract ,Drug Administration Schedule ,Cornea ,Diabetes Complications ,chemistry.chemical_compound ,Drug Delivery Systems ,Cataracts ,Glycation ,Diabetes mellitus ,medicine ,Animals ,Humans ,Histidine ,Aged ,Lubricants ,media_common ,Aged, 80 and over ,Aldehydes ,Cross-Over Studies ,Chemistry ,Carnosine ,Aminooxyacetic Acid ,Drug Synergism ,Middle Aged ,Prodrug ,medicine.disease ,Scavenger (chemistry) ,Ophthalmoscopy ,Disease Models, Animal ,Hydrazines ,Biochemistry ,Female ,Rabbits ,Ophthalmic Solutions - Abstract
In human diabetes, the deleterious effects of chronic hyperglycemia are the result of excessive nonenzymatic modification of proteins and phospholipids by glucose and its by-products leading to the formation of irreversible oxidized, aromatic, and fluorescent ligands known as advanced glycation end products. This glycation process has been associated with deleterious health effects. The present invention provides the potent inhibitors of protein glycation and AGEs formation, which are particularly advantageous for eyedrop delivery in the prevention and treatment of diabetes- and age-related pathologies.We proposed a deglycation system involving removal, by transglycation of sugar or aldehyde moieties from the Schiff bases by ophthalmic aldehyde scavenger L-carnosine derived from its ocular bioactivating sustained release prodrug 1% N-acetylcarnosine (NAC) lubricant eyedrops containing a mucoadhesive cellulose compound combined with corneal absorption promoters in drug delivery system. Carnosine analogs bearing the histidyl-hydrazide moiety were synthesized and patented in ophthalmic formulations with NAC bioactivating prodrug to moderate the enzymatic hydrolysis of a dipeptide by carnosinase (inhibited by a nonhydrolyzable substrate analog so that this keeps steadier levels of the drug active principle in the aqueous humor). Leucyl-histidylhydrazide peptidomimetic demonstrated the transglycation activity more pronounced than L-carnosine accounting for the ability of either molecule to reverse pre-existing, glycation-induced, cross-linking, and checking the nonenzymatic glycation cascade in the ophthalmic pathologies. The ophthalmic drug N-acetylcarnosine eye drop formulation with sustained time- release and increased absorption of L-carnosine in the aqueous humor (a prolonged effective dose) showed follow-up treatment efficacy for age-related cataracts for enrolled patients into the randomized double blind placebo controlled crossover clinical trial, and in over 50250 various cohort patients, was demonstrated to have an efficacy, safety and good tolerability for prevention and treatment of visual impairment in the older population data base.The bioactivating antioxidant NAC and histidyl-hydrazide are potent agents with the pleiotropic effects for ophthalmic therapy of senile cataracts and diabetic ocular complications.
- Published
- 2009
33. Mechanistic studies of amide bond scission during acidolytic deprotection of Pip containing peptide
- Author
-
Andrea Calderan, Alessio Osler, Andrea Guiotto, Paolo Ruzza, and Chiara Rubini
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Molecular Conformation ,Peptide ,Cleavage (embryo) ,Biochemistry ,SH3 domain ,pipecolic acid ,Hydrolysis ,chemistry.chemical_compound ,Structural Biology ,Drug Discovery ,Trifluoroacetic acid ,Trifluoroacetic Acid ,Peptide bond ,Molecular Biology ,Chromatography, High Pressure Liquid ,Bond cleavage ,Pipecolic acid ,Pharmacology ,chemistry.chemical_classification ,Binding Sites ,Chemistry, Physical ,Organic Chemistry ,Deuterium Exchange Measurement ,Stereoisomerism ,General Medicine ,Nuclear magnetic resonance spectroscopy ,Reference Standards ,Amides ,chemistry ,Pipecolic Acids ,peptide degradation ,Molecular Medicine ,Peptides ,TFA cleavage - Abstract
Unusual TFA catalyzed cleavage reaction is reported for peptide containing pipecolic acid residues. Although the use of TFA under standard cleavage conditions is sufficiently mild to prevent degradation of the desired products, the amide bond between consecutive pipecolic acid residues is unexpectedly hydrolyzed by standard TFA treatment. The hydrolysis is proposed to proceed via an oxazolinium ion intermediate. This mechanism is supported by H/D exchange as observed by ESI-MS and NMR experiments.
- Published
- 2008
34. A new access to quinazolines from simple anilines
- Author
-
Adriano Guiotto, Vera Barbieri, P. Manzini, Giovanni Pastorini, Giovanni Marzaro, Adriana Chilin, and Samuele Zanatta
- Subjects
Aqueous solution ,synthesis ,substituent effects ,Organic Chemistry ,General Medicine ,Biochemistry ,Combinatorial chemistry ,Potassium ferricyanide ,chemistry.chemical_compound ,chemistry ,Simple (abstract algebra) ,Drug Discovery ,Quinazoline ,Organic chemistry ,quinazoline ,Hexamethylenetetramine - Abstract
A new synthetic pathway to quinazolines is described. This new method uses hexamethylenetetramine in TFA and potassium ferricyanide in aqueous ethanolic KOH, starting from simple N-protected anilines. The method affords substituted quinazolines with high selectivities and good yields, reducing reaction-time and work-up operations.
- Published
- 2006
35. Tat cell-penetrating peptide has the characteristics of a poly(proline) II helix in aqueous solution and in SDS micelles
- Author
-
Paolo Ruzza, Alessio Osler, Gianfranco Borin, Andrea Calderan, and Andrea Guiotto
- Subjects
Protein Folding ,Circular dichroism ,Stereochemistry ,Peptide ,Biochemistry ,Micelle ,Protein Structure, Secondary ,Structural Biology ,Drug Discovery ,Organic chemistry ,peptide conformation ,Proline ,Molecular Biology ,Micelles ,poly(proline) II helix ,Pharmacology ,chemistry.chemical_classification ,Aqueous solution ,Organic Chemistry ,Sodium Dodecyl Sulfate ,Water ,Tat cell-penetrating peptide ,General Medicine ,circular dichroism ,Peptide Conformation ,Solutions ,Membrane ,chemistry ,Gene Products, tat ,Helix ,Molecular Medicine ,Peptides - Abstract
Tat cell-penetrating peptide (GRKKRRQRRRPPQG) is able to translocate and carry molecules across cell membranes. Using CD spectroscopy the conformation of this synthetic peptide was studied in aqueous and membrane-mimicking, micellar SDS solutions at different temperatures. The CD spectrum of the Tat cell-penetrating peptide in SDS micellar solution was virtually unchanged from that in aqueous solution, and at low temperature it was close to that of a poly(proline) II helix. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
- Published
- 2004
36. Protein, peptide and non-peptide drug PEGylation for therapeutic application
- Author
-
Andrea Guiotto, Gianfranco Pasut, and Francesco M. Veronese
- Subjects
Pharmacology ,Drug ,chemistry.chemical_classification ,Biochemistry ,Chemistry ,media_common.quotation_subject ,Drug Discovery ,PEGylation ,Peptide ,General Medicine ,Non peptide ,media_common - Abstract
For many years proteins have been investigated as therapeutic agents, but unfortunately their potential advantages could not be completely exploited. The main drawbacks are their intrinsic short li...
- Published
- 2004
37. 4-Hydroxymethyl- and 4-methoxymethylfuro[2,3- h ]quinolin-2(1 H )-ones: synthesis and biological properties
- Author
-
Morena Simonato, Cristina Marzano, Francarosa Baccichetti, Adriano Guiotto, and Adriana Chilin
- Subjects
Magnetic Resonance Spectroscopy ,Photochemistry ,Ultraviolet Rays ,Stereochemistry ,Guinea Pigs ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Quinolones ,Biochemistry ,Chemical synthesis ,chemistry.chemical_compound ,Drug Discovery ,Escherichia coli ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Topoisomerase II Inhibitors ,Hydroxymethyl ,Enzyme Inhibitors ,Carcinoma, Ehrlich Tumor ,Furans ,Molecular Biology ,biology ,Chemistry ,Topoisomerase ,Organic Chemistry ,DNA ,In vitro ,Furocoumarins ,Mechanism of action ,biology.protein ,Molecular Medicine ,Cattle ,Electrophoresis, Polyacrylamide Gel ,Indicators and Reagents ,medicine.symptom ,Phototoxicity ,Dermatitis, Phototoxic ,HeLa Cells ,Mutagens ,Plasmids - Abstract
4-Hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HOFQ) was prepared by a new profitable way, which allowed to synthesize also 4-methoxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (MOFQ), and 4-hydroxymethyl-6,8-dimethylfuro[2,3-h]quinolin-2(1H)-one (HOHFQ). Some biological activities of the three compounds were studied in comparison with 8-MOP. In the dark, they inhibited topoisomerase II, leading to a moderate antiproliferative activity in mammalian cells. The antiproliferative activity was also tested upon UVA irradiation in mammalian cells: all compounds showed higher activity than 8-MOP, without mutagenicity and skin phototoxicity, with the best results for HOFQ. Photobinding to DNA was investigated, demonstrating a different sequence specificity for these furoquinolinones in comparison with furocoumarins. For all these features, HOFQ and the other analogues appeared very promising photochemotherapeutic agents, whose mechanism of action will be further investigated.
- Published
- 2003
38. Dark and Photochemical Interactions of Dimethyltetrahydrobenzoangelicin with DNA
- Author
-
Sergio Caffieri, Vittorio Lucchini, Daniela Vedaldi, Adriano Guiotto, and Giorgia Miolo
- Subjects
Models, Molecular ,chemistry.chemical_classification ,Light ,Pyrimidine ,Double bond ,Photochemistry ,Stereochemistry ,Furocoumarin ,DNA ,General Medicine ,Darkness ,Ring (chemistry) ,Biochemistry ,Thymine ,chemistry.chemical_compound ,Solubility ,chemistry ,Furocoumarins ,Furan ,Physical and Theoretical Chemistry ,Uracil ,Cytosine - Abstract
A study of dark interaction and photoreaction between 4,6-dimethyltetrahydrobenzoangelicin (THBA) and DNA is described. 4,6-Dimethyltetrahydrobenzoangelicin is a furocoumarin derivative in which 4' and 5' carbons are linked by a four-methylene bridge. In spite of the bulky aliphatic ring, THBA forms a complex with DNA in the dark and, on UVA irradiation, reacts with pyrimidine bases of DNA yielding monoadducts only involving its furan side double bond. Two main photoproducts form: they derive from a C4-cycloaddition to thymine and cytosine, respectively, and account for 56% and 39% of the total photoreaction yield. Both show cis-syn configuration. Two other isomers, one with thymine and one with cytosine, formed with so much lower yield (ca 3 and 1%, respectively) that their structure could not be assigned. Furthermore, in spite of its angular structure, THBA induces a small number of crosslinks in DNA.
- Published
- 1998
39. Stearoylethanolamide exerts anorexic effects in mice via downregulation of liver stearoyl‐coenzyme A desaturase‐1 mRNA expression
- Author
-
Alberta Leon, Salvatore Terrazzino, Adriano Guiotto, Fiorenzo Berto, Maurizio Dalle Carbonare, Michele Fabris, and Daniele Bernardini
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Coenzyme A ,Administration, Oral ,Down-Regulation ,Biology ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Mice ,chemistry.chemical_compound ,Oleoylethanolamide ,Downregulation and upregulation ,Internal medicine ,N-Acylethanolamine ,Genetics ,medicine ,Animals ,Ethanolamide ,RNA, Messenger ,Molecular Biology ,Dose-Response Relationship, Drug ,Leptin ,digestive, oral, and skin physiology ,Stearoylethanolamide ,food and beverages ,Feeding Behavior ,Anorexia ,Endocrinology ,Liver ,chemistry ,Ethanolamines ,lipids (amino acids, peptides, and proteins) ,Cannabinoid ,Food Deprivation ,Injections, Intraperitoneal ,Stearic Acids ,Stearoyl-CoA Desaturase ,Biotechnology - Abstract
Given the recent demonstration that oleoylethanolamide (OEA), a cannabinoid receptor-inactive N-acylethanolamine, decreases food intake by activating the nuclear receptor PPARalpha (peroxisome proliferator-activated receptor alpha) in the periphery, we here evaluated the effects of both saturated and unsaturated C18 N-acylethanolamides (C18:0; C18:1; C18:2) in mice feeding behavior after overnight starvation. Our results show stearoylethanolamide (SEA, C18:0) exerts, unlike other unsaturated C18 homologs, a marked dose-dependent anorexic effect evident already at 2 h after its intraperitoneal administration. In addition, oral administration of SEA (25 mg/kg) was also effective in reducing food consumption, an effect ascribed to the molecule itself and not to its catabolites. Moreover, although the anorexic response to oral administered SEA was not associated with changes in the levels of various hematochemical parameters (e.g., glucose, cholesterol, triglycerides, leptin) nor in liver mRNA expression of peroxisome proliferator-activated receptors (PPARs) including PPARalpha, the anorexic effect of SEA was interestingly accompanied by a reduction in liver stearoyl-CoA desaturase-1 (SCD-1) mRNA expression. As SCD-1 has been recently proposed as a molecular target for the treatment of obesity, the novel observation provided here that SEA reduces food intake in mice in a structurally selective manner, in turn, correlated with downregulation of liver SCD-1 mRNA expression, has the potential of providing new insights on a class of lipid mediators with suitable properties for the pharmacological treatment of over-eating dysfunctions.
- Published
- 2004
40. Efficient and chemoselective N-acylation of 10-amino-7-ethyl camptothecin with poly(ethylene glycol)
- Author
-
Francesco M. Veronese, Christine Deuschel, Andrea Guiotto, Piero Orsolini, Seigo Sawada, Takeshi Yaegashi, Akinobu Kurita, Takeshi Matsuzaki, Norimasa Kaneda, Mirta Canevari, and Olivier Lavanchy
- Subjects
Stereochemistry ,Acylation ,Clinical Biochemistry ,Pharmaceutical Science ,Camptothecin Analogue ,Biochemistry ,Polyethylene Glycols ,chemistry.chemical_compound ,Drug Discovery ,PEG ratio ,polycyclic compounds ,medicine ,heterocyclic compounds ,Chemoselectivity ,neoplasms ,Molecular Biology ,Tetrapeptide ,Organic Chemistry ,Stereoisomerism ,chemistry ,Molecular Medicine ,Camptothecin ,biological phenomena, cell phenomena, and immunity ,Ethylene glycol ,Conjugate ,medicine.drug - Abstract
A new poly(ethylene glycol) (PEG) conjugate of 10-amino-7-ethyl camptothecin, a potent antitumor analogue of camptothecin, has been synthesized and preliminary in vivo tests have been performed. Successful chemoselective N-acylation of 10-amino-7-ethyl camptothecin was accomplished using phenyl dichlorophosphate, a coupling reagent used in esterification of alcohols, while other coupling methods failed, due to the low nucleophilicity of the amino group in position 10. The conjugate was tested against P388 murine leukemia cell lines and resulted equipotent to CPT-11, a camptothecin analogue already in clinical use.
- Published
- 2004
41. Development of a novel furocoumarin derivative inhibiting NF-κB dependent biological functions: design, synthesis and biological effects
- Author
-
Adriano Guiotto, Francesco Dall'Acqua, Roberto Gambari, Irene Mancini, Giovanni Marzaro, Ilaria Lampronti, Adriana Chilin, Monica Borgatti, Nicoletta Bianchi, and Laura Piccagli
- Subjects
Virtual screening ,Models, Molecular ,Cystic Fibrosis ,In silico ,Furocoumarin ,Cystic fibrosis ,Interleukin-8 ,Docking ,Cell Line ,chemistry.chemical_compound ,Furocoumarins ,Drug Discovery ,Gene expression ,Humans ,RNA, Messenger ,Pharmacology ,Tumor Necrosis Factor-alpha ,Organic Chemistry ,NF-kappa B ,Biological activity ,General Medicine ,DNA ,Molecular biology ,IκBα ,Biochemistry ,chemistry ,Gene Expression Regulation ,Docking (molecular) ,Drug Design ,Protein Binding - Abstract
Nuclear Factor kappaB (NF-κB) plays a very important role in the control of gene expression and is deeply involved in several human pathologies. Accordingly, molecules targeting NF-κB dependent biological functions are considered of great interest. Virtual screening of furocoumarin libraries against NF-κB p50 allowed to rank compounds in respect to their expected ability to bind NF-κB and the identified compound might be considered for the development of analogs to be tested for biological activity on inhibition of NF-κB/DNA complex formation. The data reported in the present paper suggest that, following this approach, the best ranked compounds identified by virtual screening (a) strongly bind in silico to NF-κB and (b) efficiently inhibit the molecular interactions between 32P-labeled NF-κB double stranded DNA and p50 or p50/p65 complex. These data allowed to develop a novel lead of great interest for inhibiting NF-κB dependent biological functions. This novel molecule (compound 2), bearing a methyl group in the 9 position of the psoralen nucleus, exhibits high efficiency in inhibiting NF-κB/DNA interactions. In addition, we found that compound 2 is a potent inhibitor of IL-8 gene expression in TNF-α treated IB3-1 cystic fibrosis cells. Taken together, our data indicate that compound 2 might find an important place in the set of molecules of interest for the development of pharmaceutical strategies against the inflammatory phenotype of cystic fibrosis.
- Published
- 2011
42. Using the TOPS-MODE approach to fit multi-target QSAR models for tyrosine kinases inhibitors
- Author
-
Ignazio Castagliuolo, Humberto González-Díaz, Adriano Guiotto, Francesca Tonus, Adriana Chilin, Paola Brun, Giovanni Marzaro, and Eugenio Uriarte
- Subjects
Models, Molecular ,Quantitative structure–activity relationship ,Molecular model ,Quantitative Structure-Activity Relationship ,Structure-Activity Relationship ,Multi target ,Drug Discovery ,Protein Kinase Inhibitors ,Tyrosine kinase inhibitors ,Pharmacology ,Activity profile ,Molecular Structure ,QSAR ,Chemistry ,Drug discovery ,Organic Chemistry ,Stereoisomerism ,General Medicine ,Protein-Tyrosine Kinases ,TOPS-MODE ,Quinazolines ,Tops mode ,Biochemistry ,Signal transduction ,Tyrosine kinase - Abstract
Tyrosine kinases constitute an eligible class of target for novel drug discovery. They resulted often overexpressed and/or deregulated in several cancer diseases. Thus, the development of novel tyrosine kinases inhibitors is of value, as well as the finding of novel cheminformatic tools for their design. Among the different ways to rationally design novel compounds, the Quantitative Structure-Activity Relationship (QSAR) plays a key role. The QSAR approach, in fact, allow the prediction of activity against a number of targets (multi-target QSAR), thus leading to models able to predict not only the activity of a compound, but also its selectivity versus a set of targets. Despite it is well known that tyrosine kinase inhibitors have to show multi-kinases inhibitory potency to be useful in anticancer therapy, only few multi-target computational tools have been developed to help medicinal chemists in the design of novel compounds. Herein we present the development of several multi-target classification QSAR (mtc-QSAR) models useful to assess the activity profile of the tyrosine kinases inhibitors.
- Published
- 2010
43. ChemInform Abstract: Pyrroloquinolinone Methylderivatives, Furocoumarin Analogues: Synthesis and Biological Activity
- Author
-
F. Baccichetti, Paolo Rodighiero, Cristina Marzano, Adriana Chilin, A. Guiotto, P. Manzini, F. Carlassare, Franco Bordin, and A. Castellin
- Subjects
Infectivity ,biology ,Stereochemistry ,DNA damage ,Furocoumarin ,Biological activity ,General Medicine ,biology.organism_classification ,In vitro ,HeLa ,chemistry.chemical_compound ,Biochemistry ,chemistry ,Protein biosynthesis ,DNA - Abstract
Searching new photochemotherapeutic agents, a series of methylpirroloquinolinones were prepared by a new synthetic pathway, thus univocally obtaining the title compounds. The photobiological activity of some of these compounds was assayed; upon UVA activation, a marked capacity of inhibiting macromolecular synthesis in Ehrlich cells was observed, which appeared to be markedly high testing protein synthesis. Pyrroloquinolinones induced a strong inhibition of the clonal growing capacity of HeLa cells cultivated in vitro. Studying DNA photodamage in HL60 cells high amounts of single strand breaks and DNA-protein cross-links were detected. Pyrroloquinolines inhibited T2 bacteriophage infectivity, but induced no significant amounts of revertants in E. coli WP2 TM9, a strain very sensitive to DNA damage. On the contrary, 8-MOP, tested in the same experimental conditions exhibited an evident photomutagenecity. These data suggest that pyrroloquinolines induced antiproliferative effects by a mechanism in which DNA-photobinding practically does not takes place, and therefore different from that shown by known furocoumarins. Pyrroloquinolinones showed also a moderate antiproliferative activity in the dark.
- Published
- 2010
44. Exploring epidermal growth factor receptor (EGFR) inhibitor features: the role of fused dioxygenated rings on the quinazoline scaffold
- Author
-
Adriano Guiotto, Luca Urbani, Giovanni Marzaro, Francesca Tonus, Pier Paolo Parnigotto, Adriana Chilin, and Maria Teresa Conconi
- Subjects
CANCER-THERAPY ,Stereochemistry ,Antineoplastic Agents ,Dioxanes ,chemistry.chemical_compound ,Mice ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,BINDING ,Quinazoline ,TYROSINE KINASE INHIBITORS ,Structure–activity relationship ,Animals ,Humans ,Epidermal growth factor receptor ,Phosphorylation ,EGFR inhibitors ,Cell Proliferation ,chemistry.chemical_classification ,biology ,POTENT ,Aromatic amine ,Biological activity ,Dioxolanes ,TYROSINE KINASE INHIBITORS, CANCER-THERAPY, BINDING, POTENT, CELLS ,In vitro ,ErbB Receptors ,Biochemistry ,chemistry ,Epidermoid carcinoma ,CELLS ,Oxepins ,biology.protein ,NIH 3T3 Cells ,Quinazolines ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Heterocyclic Compounds, 3-Ring - Abstract
A number of dioxolane, dioxane, and dioxepine quinazoline derivatives have been synthetized and evaluated as EGFR inhibitors. Their cytotoxic activity has been tested against two cell lines overexpressing and not expressing EGFR. Most derivatives were able to counteract EGF-induced EGFR phosphorylation, and their potency was comparable to the reference compound PD153035. The size of the fused dioxygenated ring was crucial for the biological activity, the dioxane derivatives being the most promising class of this series.
- Published
- 2010
45. A novel approach to quinazolin-4(3H)-one via quinazoline oxidation: an improved synthesis of 4-anilinoquinazolines
- Author
-
Giovanni Pastorini, Giovanni Marzaro, Adriana Chilin, and Adriano Guiotto
- Subjects
Quinazoline derivatives ,biology ,Stereochemistry ,Chemistry ,Organic Chemistry ,tyrosine kinase ,Ring (chemistry) ,Biochemistry ,Chemical synthesis ,High yielding ,anilinoquinazoline ,chemistry.chemical_compound ,Enzyme inhibitor ,quinazoline oxidation ,Drug Discovery ,Protein-Tyrosine Kinases ,Quinazoline ,biology.protein ,Tyrosine kinase - Abstract
A novel strategy to prepare 4-anilinoquinazoline derivatives based on the oxidation of the quinazoline ring is described. Quinazoline oxidation has been investigated and improved, thus leading to an efficient and high yielding method to quinazolin-4(3H)-ones. Efficiency of this approach has been evaluated synthesizing four well known tyrosine kinase inhibitors and comparing the obtained yields with those achievable through conventional synthetic methods.
- Published
- 2010
46. Structure and reactivity of molecular ions of isomeric pyrrolquinolinones and benzoquinolizinones
- Author
-
O. Curcuruto, Adriano Guiotto, A. Castellin, Pietro Traldi, S. Fontana, A. Chilin, and Paolo Rodighiero
- Subjects
Stereochemistry ,Chemistry ,Mass spectrometry ,Kinetic energy ,Biochemistry ,Ion trapping ,Ion ,Fragmentation (mass spectrometry) ,Computational chemistry ,Molecular Medicine ,Ion trap ,Instrumentation ,Isomerization ,Spectroscopy ,Electron ionization - Abstract
The structure and mass spectrometric behaviour of molecular species of two benzo [ij] quinolizin-5-ones and one pyrrol [3,2,1-ij] quinolin4-one were studied in detail with the aid of mass-analysed ion kinetic energy spectrometry and ion trapping experiments. Whereas in the usual electron impact spectra obtained with a double-focusing instrument clear differences are present among the three isomeric componds, the unimolecular fragmentation processes of the related M +. indicate the occurrence of isomerization processes to give a common structure
- Published
- 1992
47. BIOLOGICAL PROPERTIES OF SOME BENZOPSORALEN DERIVATIVES
- Author
-
Franca Majone, Adriano Guiotto, Franco Bordin, Francarosa Baccichetti, A Capozzi, Maria Teresa Conconi, and F. Carlassare
- Subjects
Aphidicolin ,Ultraviolet Rays ,DNA polymerase ,8-METHOXYPSORALEN ,CHO Cells ,MUTAGENICITY ,Biochemistry ,Mice ,chemistry.chemical_compound ,Cricetinae ,Furocoumarins ,Animals ,Physical and Theoretical Chemistry ,Carcinoma, Ehrlich Tumor ,biology ,DNA synthesis ,PHOTOCHEMISTRY ,Chinese hamster ovary cell ,Topoisomerase ,Biological activity ,DNA ,General Medicine ,Darkness ,8-METHOXYPSORALEN, PHOTOCHEMOTHERAPY, FUROCOUMARINS, PSORALENS, PHOTOCHEMISTRY, MUTAGENICITY, CELLS, DNA ,In vitro ,Photochemotherapy ,chemistry ,CELLS ,biology.protein ,PSORALENS - Abstract
The biological activity of some benzopsoralen derivatives, prepared with the aim of obtaining new drugs for photochemotherapy, has been studied. The more interesting compounds are 4-hydroxymethyl-4',5'-benzopsoralen and 4-hydroxymethyl-4',5'-tetrahydro-benzopsoralen, which were found to be active in the dark also: DNA and RNA synthesis were both inhibited in Ehrlich cells, even if in a partially reversible fashion, while protein synthesis remained unaffected. In Chinese hamster ovary cells cultured in vitro, the clonal growth was strongly inhibited by incubation in the dark with both drugs, while a number of chromosomal aberrations was observed in the fraction of growing cells. Using alkaline elution, DNA strand breaks were detected. In addition, in the presence of aphidicolin, a specific inhibitor of DNA polymerase, the clonal growing capacity was completely restored; in contrast, the number of DNA strand breaks remained unchanged. All these results suggest that DNA topoisomerases are probably the target of these two benzopsoralens. These compounds are also good sensitizers; by UV-A irradiation they have a good capacity to produce singlet oxygen, but they appeared to be unable to induce erythemas on guinea-pig skin. Under UV-A light, they induced a strong inhibition of DNA synthesis in Ehrlich cells. Thus, benzopsoralens appear to be capable of inducing strong antiproliferative effects by two different mechanisms, by UV-A irradiation and in the dark.
- Published
- 1992
48. 4, 4', 5'-TRIMETHYL-8-AZAPSORALEN, A NEW-PHOTOREACTIVE AND NON-SKIN-PHOTOTOXIC BIFUNCTIONAL BIOISOSTER OF PSORALEN
- Author
-
Adriano Guiotto, Franco Bordin, Adriana Chilin, Sergio Caffieri, Daniela Vedaldi, Francesco Dall'Acqua, Francarosa Baccichetti, and Francesco Carlassare
- Subjects
DNA Replication ,Radiation-Sensitizing Agents ,Photochemistry ,Ultraviolet Rays ,Stereochemistry ,Guinea Pigs ,Biochemistry ,DNA Synthesis Inhibition ,Guinea pig ,Mice ,chemistry.chemical_compound ,Furocoumarins ,Escherichia coli ,Animals ,Physical and Theoretical Chemistry ,Carcinoma, Ehrlich Tumor ,Bifunctional ,Psoralen ,Skin ,Singlet Oxygen ,DNA synthesis ,Mutagenicity Tests ,DNA ,General Medicine ,Oxygen ,chemistry ,Yield (chemistry) ,Phototoxicity ,DNA Damage - Abstract
— Photochemical and photobiological properties of a new isoster of psoralen, 4, 4′, 5′-trimethyl-8-azapsoralen (4, 4′, 5′-TMAP), have been studied. This compound shows a high DNA-photobinding rate, higher than that of 8-methoxypsoralen (8-MOP), forming both monoadducts and inter-strand cross-links. The yield of cross-links, however, is markedly lower than that of 8-MOP. Antiproliferative activity of 4, 4′, 5′-TMAP, in terms of DNA synthesis inhibition in Ehrlich ascites tumor cells, is higher than that of 8-MOP. Mutagenic activity on E. coli WP2 R46+ cells appeared similar to or even lower than that of 8-MOP. This new compound applied on depilated guinea pig skin and irradiated with UVA did not show any skin-phototoxicity. On the basis of these properties 4, 4′, 5′-TMAP appears to be a potential photochemotherapeutic agent.
- Published
- 1991
49. Synthesis and antitumor activity of novel amsacrine analogs: the critical role of the acridine moiety in determining their biological activity
- Author
-
Giovanni Marzaro, Adriano Guiotto, Lisa Dalla Via, Christine Marzano, Adriana Chilin, Maria Grazia Ferlin, and Giovanni Pastorini
- Subjects
Amsacrine ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Amsacrine analogs ,DNA ,Pyranoquinoline ,anticancer drugs ,Biochemistry ,Chemical synthesis ,chemistry.chemical_compound ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,medicine ,Moiety ,Structure–activity relationship ,Humans ,Molecular Biology ,Cell Proliferation ,Sulfonamides ,Organic Chemistry ,Quinoline ,Biological activity ,Intercalating Agents ,chemistry ,Epidermoid carcinoma ,Acridine ,Molecular Medicine ,medicine.drug - Abstract
A new series of N-[4-(2'-oxo-2H-pyrano[2,3-b]quinolin-5'-ylamino)-phenyl]-methanesulfonamides was prepared and analyzed as novel amsacrine-like derivatives. Our preliminary biological evaluation has shown that the replacement of the acridine moiety with the analogous 2-oxo-2H-pyrano[2,3-b]quinoline system drastically reduced both their anticancer activity and their propency to intercalate into double stranded DNA.
- Published
- 2008
50. Coumarin as attractive casein kinase 2 (CK2) inhibitor scaffold: an integrate approach to elucidate the putative binding motif and explain structure-activity relationships
- Author
-
Giuseppe Zagotto, A. Guiotto, Adriana Chilin, Eugenio Uriarte, Samuele Zanatta, Andrea Bortolato, Stefano Moro, Roberto Battistutta, Flavio Meggio, Marco Mazzorana, Giorgio Cozza, Lorenzo A. Pinna, and Giorgia Poletto
- Subjects
Quantitative structure–activity relationship ,Virtual screening ,animal structures ,Binding Sites ,Molecular model ,Chemistry ,fungi ,Amino Acid Motifs ,Crystallography, X-Ray ,Zea mays ,Structure-Activity Relationship ,Biochemistry ,Chromones ,Coumarins ,Drug Discovery ,Molecular Medicine ,Transferase ,Thermodynamics ,Casein kinase 2 ,Signal transduction ,Binding site ,Protein kinase A ,Casein Kinase II ,Protein Binding - Abstract
Casein kinase 2 (CK2) is an ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Recently, using different virtual screening approaches, we have identified several novel CK2 inhibitors. In particular, we have discovered that coumarin moiety can be considered an attractive CK2 inhibitor scaffold. In the present work, we have synthetized and tested a small library of coumarins (more than 60), rationalizing the observed structure–activity relationship. Moreover, the most promising inhibitor, 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC), has been also crystallized in complex with CK2, and the experimental binding mode has been used to derive a linear interaction energy (LIE) model.
- Published
- 2008
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