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HPLC-MS/MS method for simultaneous analysis of plasma 2-hydroxybuty-rate and 2-hydroxyisobutyrate: Development and clinical significance

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CLINICA CHIMICA ACTA 2025年 565卷 120023页

作者： Campi, Beatrice vitelli, valentina Saponaro, Federica Zucchi, Riccardo Ferrannini, Ele Saba, Alessandro CNR Inst Clin Physiol Via Giuseppe Moruzzi 1 I-56124 Pisa Italy Univ Pisa Dept Surg Med & Mol Pathol & Crit Care Med Via Savi 10 I-56126 Pisa Italy Univ Pisa Ctr Instrument Sharing Lungarno Pacinotti 43-44 I-56126 Pisa Italy

Recent studies have identified relationships between diabetes mellitus and short-chain fatty acids, including 2hydroxybutyrate (2-HB) and 2-hydroxyisobutyrate (2-HiB);2-HB has been associated to the early stages of insulin resistance, while 2-HiB with the risk and progression of complications of Type 1 diabetes. Their metabolism and pathophysiological role in humans are not fully clarified. The possible association between 2-HB and 2-HiB and diabetes mellitus was investigated with a novel mass spectrometry-based assay, capable of discriminating plasma 2-HiB and 2-HB from their HB isomers. Accuracy and precision (RSD%) were always in the range 99-102% and 0.7-3.5%, respectively. The study involved samples from subjects with normal glucose tolerance (NGT) and Type 2 diabetes (T2D), originally included in a multicenter study investigating mechanisms involved in atherothrombosis. NGT subjects exhibited concentrations of 2-HB and 2-HiB of 61 (36) and 3.1 (1.9) mu mol/L, median (interquartile range), respectively, that were significantly lower than those of the T2D patients, whose values were 74 (4.0) and 3.8 (2.9) mu mol/L, respectively. The pattern of association of these molecules with clinical and metabolic variables is partially different: both compounds were directly related to male sex, BMI, HbA1c, and plasma glucose, 2-HiB also with age, systolic blood pressure, and HDL-cholesterol. Furthermore, they correlate with free fatty acids, glycerol, and triglyceride concentrations, but the latter correlation was negative for 2-HB and positive for 2-HiB. Results confirmed the clinical significance of 2-HB and 2-HiB, in differential association with metabolic features of T2D.

关键词： 2-hydroxybutyrate 2-hydroxyisobutyrate HPLC Mass spectrometry

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Development and primary characterization of a human thyroid organoid in vitro model for thyroid metabolism investigation

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MOLECULAR AND CELLULAR ENDOCRINOLOGY 2024年 594卷 112377页

作者： Cristiani, Sofia Bertolini, Andrea Carnicelli, Vittoria Contu, Lucia vitelli, valentina Saba, Alessandro Saponaro, Federica Chiellini, Grazia Sabbatini, Antonietta Raffaella Maria Giambelluca, Maria Anita Lenzi, Paola Fornai, Francesco Rossi, Leonardo Materazzi, Gabriele Ambrosini, Carlo Enrico Rutigliano, Grazia Zucchi, Riccardo Bizzarri, Ranieri Ghelardoni, Sandra Univ Pisa Dept Surg Med Mol Pathol & Crit Area Via Roma 57 I-56126 Pisa Italy Univ Pisa Dept Translat Res & New Technol Med & Surg Via Roma 55 I-56126 Pisa Italy Ist Ricovero & Cura Carattere Sci IRCCS Neuromed I-86077 Pozzilli Italy Univ Hosp Pisa Endocrine Surg Unit Pisa Italy Kings Coll London Inst Psychiat Psychol & Neurosci London England

A 3D thyroid model was developed to address the limitations of 2D cultures and study the effects of compounds like 3-MNT on dehalogenase 1 (IYD) and metabolic activity. Morphology was assessed by TEM, and the expression of tissue-specific genes (TPO, TSHR, PAX8, TTF-1, NIS, IYD, TG) and metabolic features were analyzed using qRT-PCR, immunofluorescence, western blotting, ELISA, and LC-MS/MS, with and without TSH stimulus and 3-MNT treatment. Confocal and TEM analyses confirmed a follicle-like 3D structure. Expression of TPO, NIS, TG, TSH, and PAX markers was significantly higher (p < 0.05) in 3D versus 2D cultures, and ELISA showed increased TG protein production. 3-MNT treatment inhibited IYD activity, indicated by increased MIT and DIT in the media, and significantly altered (p < 0.05) NIS, TG, IYD, TSHR, and TPO expression. These findings suggest 3D thyroid cultures closely replicate tissue traits and functionality, providing a valuable tool for thyroid research.

关键词： Thyroid Organoid TSH IYD 3-MNT Disruptors

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Treatment for pulmonary hypertension of left heart disease

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Current Treatment Options in Cardiovascular Medicine 2012年第4期14卷 319-327页

作者： Guazzi, Marco vitelli, Alessandra Labate, valentina Arena, Ross Cardiopulmonary Unit University of Milano Policlinico San Donato 20097 Milano Piazza Malan 2 Italy Rehabilitation Unit Federico II University Naples Italy Physical Therapy Program Department of Orthopaedics University of New Mexico Albuquerque NM 87131-5271 United States Division of Cardiology Department of Internal Medicine University of New Mexico Albuquerque NM 87131-5271 United States

Pulmonary hypertension (PH) secondary to left heart disease is a largely underestimated target of therapy. Except for a specific focus on PH consequences in patients with advanced heart failure (HF) receiving a left ventricular mechanical assist device or candidates for transplantation, prevention and treatment of initial subclinical forms of PH are not considered a priority in the management of this chronic disease population. Nonetheless, there is recent growing evidence supporting a clinical and prognostic role of PH in the elderly and in HF with preserved ejection fraction (pEF). Studies have defined PH-HFpEF as a new entity typically defining the evolving nature of disease. Although the prevalence of PH in these populations is not well-defined, the potential for effective pharmacological approaches that might impact the natural history of the disease starting from earlier stages is promising. However, it should be recognized that pharmacological studies performed to date with traditional pulmonary vasodilators in cohorts with HF and left-sided PH have not been positive, primarily because of concomitant systemic hypotension and hepatic side effects. This evidence along with the lack of studies specifically performed in the elderly and HFpEF often lead Guidelines to give neutral recommendations or even arbitrary assumptions. Recent availability of selective well-tolerated pulmonary vasodilators, such as phosphodiesterase type 5 (PDE5) inhibitors, however, seem to offer a solid background for treating left-sided PH at both early and later stages of the disease process. © Springer Science+Business Media, LLC 2012.

关键词： Cardiac resynchronization therapy Endothelin-1 receptor blockers Heart failure LV assist devices Nitric oxide PDE-5 inhibitors Prostaglandins Pulmonary hypertension Pulmonary vasodilators

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Minimizing the Access Trauma of Laparoscopic Sleeve Gastrectomy: the Transoral Specimen Extraction Technique

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OBESITY SURGERY 2016年第1期26卷 229-233页

作者： Lirici, Marco Maria Romeo, valentina Simonelli, Luigi Tierno, Simone vitelli, Carlo Eugenio San Giovanni Hosp Dept Surg I-00182 Rome Italy Policlin Umberto 1 DEA I-00161 Rome Italy

Laparoscopic sleeve gastrectomy has become a popular stand-alone procedure among bariatric surgeons. Recently, Natural Orifice Specimen Extraction laparoscopic surgery has been introduced to avoid minilaparotomy, possibly reducing postoperative pain, hospital stay, and improving QoL and cosmetics. Operative steps and preliminary results of NOSE sleeve gastrectomy are described and reported. Five patients underwent NOSE LSG from November 2014 to March 2015. Selection criteria were as follows: age < 60 years, ASA score a parts per thousand currency signIII, BMI < 50. Operative steps are the same of standard LSG, but the stomach transection that starts higher on the greater curvature. A 2-3 cm width opening is created on the exceeding antrum and the resected stomach sutured to the calibration probe tip, which is pull back allowing transoral specimen extraction. The exceeding antrum is stapler-trimmed, allowing breach closure and completion of tubulization. Mean age was 41.6 years (median 43), average weight was 123.6 Kg (median 114), mean BMI 43.6 Kg/m(2) (median 44). Mean operation time was 72 min (median 75). Mean and median postoperative stay were 4.6 and 5. No intraoperative nor postoperative complications occurred. Postoperative day 1 mean and median VAS pain score at were 1.4 and 1, respectively. Follow-up ranged 1-5 months (mean and median 3), average weight loss was 19.8 Kg (median 19), and excess weight loss 36.2 % (median 32 %). NOSE LSG potential advantages are as follows: improved cosmetics, decreased postoperative pain, possible incisional hernia rate reduction. No objective data are available to confirm these theoretical benefits;larger observational studies and RCTs are mandatory before clinical validation.

关键词： Laparoscopic sleeve gastrectomy NOSE Natural orifice specimen extraction NOSE sleeve gastrectomy Transoral specimen extraction Transgastric specimen extraction Reduced port surgery

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Polythelia: Still a marker of urinary tract anomalies in children?

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SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY 2009年第1期43卷 47-50页

作者： Ferrara, Pietro Giorgio, valentina vitelli, Ottavio Gatto, Antonio Romano, Valerio Del Bufalo, Francesca Nicoletti, Alessandro Catholic Univ A Gemelli Hosp Dept Pediat I-00168 Rome Italy Campus Biomed Univ Rome Italy

Objective. Supernumerary nipples (SNN), or polythelia, are the most common form of the accessory mammary tissue malformation. The frequency of this condition ranges from 0.2% to 5.6% depending on various factors. This condition is associated with several anomalies, although this association is often controversial. The aim of this study was to evaluate the association between SNN and kidney/urinary tract (K/UT) anomalies, where anomalies is taken to mean functional disorders, malformations and diseases. Material and methods. A case-control study was performed. The study evaluated 166 children (case group) referred to the Pediatric Nephrology Unit of the Department of Pediatrics of the Catholic University of Rome and 182 children (control group) admitted to the Department of Pediatrics because of pathologies not involving the urinary tract. Results. There were 11 children with SNN in the case group, and only two patients in the control group (6.62% vs 1.09%, p0.05). Conclusion. The results show a high incidence of K/UT anomalies in children with SNN, and therefore K/UT should be investigated in this specific population.

关键词： Children supernumerary nipples urinary tract anomalies

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BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment

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NATURE COMMUNICATIONS 2018年第1期9卷 5376页

作者： D'Alessandro, Giuseppina Whelan, Donna Rose Howard, Sean Michael vitelli, Valerio Renaudin, Xavier Adamowicz, Marek Iannelli, Fabio Jones-Weinert, Corey Winston Lee, MiYoung Matti, valentina Lee, Wei Ting C. Morten, Michael John Venkitaraman, Ashok Raraakrishnan Cejka, Petr Rothenberg, Eli di Fagagna, Fabrizio d'Adda FIRC Inst Mol Oncol IFOM Via Adamello 16 I-20139 Milan Italy NYU Sch Med Dept Biochem & Mol Pharmacol New York NY 10016 USA Univ Svizzera Italiana Inst Res Biomed Via Vela 6 CH-6500 Bellinzona Switzerland Univ Cambridge Med Res Council Canc Unit Hills Rd Cambridge CB2 0XZ England Swiss Fed Inst Technol Inst Biochem Dept Biol Otto Stern Weg 3 CH-8093 Zurich Switzerland CNR IGM Via Abbiategrasso 207 I-27100 Pavia Italy Univ Sussex Sch Life Sci Genome Damage & Stabil Ctr Brighton BN1 9RH E Sussex England

DNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase cells, dilncRNAs pair to the resected DNA ends and form DNA: RNA hybrids, which are recognized by BRCA1. We also show that BRCA2 directly interacts with RNase H2, mediates its localization to DSBs in the S/G2 cell-cycle phase, and controls DNA: RNA hybrid levels at DSBs. These results demonstrate that regulated DNA: RNA hybrid levels at DSBs contribute to HRmediated repair.

关键词： Cancer Cell biology

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Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks

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NATURE CELL BIOLOGY 2017年第12期19卷 1400-+页

作者： Michelini, Flavia Pitchiaya, Sethuramasundaram vitelli, Valerio Sharma, Sheetal Gioia, Ubaldo Pessina, Fabio Cabrini, Matteo Wang, Yejun Capozzo, Ilaria Iannelli, Fabio Matti, valentina Francia, Sofia Shivashankar, G. V. Walter, Nils G. di Fagagna, Fabrizio d'Adda IFOM I-20139 Milan Italy Univ Michigan Dept Chem Single Mol Anal Grp Ann Arbor MI 48109 USA Univ Michigan Ctr RNA Biomed Dept Chem Ann Arbor MI 48109 USA CNR Ist Genet Mol I-27100 Pavia Italy Natl Univ Singapore Mechanobiol Inst Singapore 117411 Singapore Univ Michigan Ctr Canc Michigan Ctr Translat Pathol Ann Arbor MI 48109 USA

The DNA damage response (DDR) preserves genomic integrity. Small non-coding RNAs termed DDRNAs are generated at DNA double-strand breaks (DSBs) and are critical for DDR activation. Here we show that active DDRNAs specifically localize to their damaged homologous genomic sites in a transcription-dependent manner. Following DNA damage, RNA polymerase II (RNAPII) binds to the MRE11-RAD50-NBS1 complex, is recruited to DSBs and synthesizes damage-induced long non-coding RNAs (dilncRNAs) from and towards DNA ends. DilncRNAs act both as DDRNA precursors and by recruiting DDRNAs through RNA-RNA pairing. Together, dilncRNAs and DDRNAs fuel DDR focus formation and associate with 53BP1. Accordingly, inhibition of RNAPII prevents DDRNA recruitment, DDR activation and DNA repair. Antisense oligonucleotides matching dilncRNAs and DDRNAs impair site-specific DDR focus formation and DNA repair. We propose that DDR signalling sites, in addition to sharing a common pool of proteins, individually host a unique set of site-specific RNAs necessary for DDR activation.

关键词： DNA damage and repair Double-strand DNA breaks Non-coding RNAs Transcription

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Anti-EphA2 Antibodies with Distinct In Vitro Properties Have Equal In Vivo Efficacy in Pancreatic Cancer

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JOURNAL OF ONCOLOGY 2009年第1期2009卷 951917页

作者： Ansuini, Helenia Meola, Annalisa Gunes, Zeynep Paradisi, valentina Pezzanera, Monica Acali, Stefano Santini, Claudia Luzzago, Alessandra Mori, Federica Lazzaro, Domenico Ciliberto, Gennaro Nicosia, Alfredo La Monica, Nicola vitelli, Alessandra Ist Ric Biol Mol P Angeletti I-00040 Rome Italy CSIC IBMB E-08028 Barcelona Spain Okairos I-00040 Rome Italy

The EphA2 receptor tyrosine kinase is overexpressed in a variety of human epithelial cancers and is a determinant of malignant cellular behavior in pancreatic adenocarcinoma cells. Moreover, it is expressed in tumor endothelium and its activation promotes angiogenesis. To better clarify the therapeutic potential of monoclonal antibodies (mAbs) directed to the EphA2 receptor, we generated a large number of mAbs by differential screening of phage-Ab libraries by oligonucleotide microarray technology and implemented a strategy for the rapid identification of antibodies with the desired properties. We selected two high-affinity and highly specific EphA2 monoclonal antibodies with different in vitro properties on the human pancreatic tumor cell line MiaPaCa2. One is a potent EphA2-agonistic antibody, IgG25, that promotes receptor endocytosis and subsequent degradation, and the second is a ligand antagonist, IgG28, that blocks the binding to ephrin A1 and is cross-reactive with the mouse EphA2 receptor. We measured the effect of antibody treatment on the growth of MiaPaCa2 cells orthotopically transplanted in nude mice. Both IgG25 and IgG28 had strong antitumor and antimetastatic efficacy. In vivo treatment with IgG25 determined the reduction of the EphA2 protein levels in the tumor and the phosphorylation of FAK on Tyr576 while administration of IgG28 caused a decrease in tumor vascularization as measured by immunohistochemical analysis of CD31 in tumor sections. These data show that in a pancreatic cancer model comparable therapeutic efficacy is obtained either by promoting receptor degradation or by blocking receptor activation. Copyright (C) 2009 Helenia Ansuini et al.

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Response of the imaging cameras to hard radiation during JET operation

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FUSION ENGINEERING AND DESIGN 2017年 123卷 669-673页

作者： Huber, Alexander Sergienko, Gennady Kinna, David Huber, valentina Milocco, Alberto Mercadier, Laurent Balboa, Itziar Conroy, Sean Cramp, Simon Kiptily, Vasili Kruezi, Uron Lambertz, Horst Toni Linsmeier, Christian Matthews, Guy Popovichev, Sergey Mertens, Philippe Silburn, Scott Zastrow, Klaus-Dieter Abhangi, M. Abreu, P. Aftanas, M. Afzal, M. Aggarwal, K. M. Aho-Mantila, L. Ahonen, E. Aints, M. Airila, M. Albanese, R. Alegre, D. Alessi, E. Aleynikov, P. Alfier, A. Alkseev, A. Allan, P. Almaviva, S. Alonso, A. Alper, B. Alsworth, I. Alves, D. Ambrosino, G. Ambrosino, R. Amosov, V. Andersson, F. Andersson Sunden, E. Angelone, M. Anghel, A. Anghel, M. Angioni, C. Appel, L. Apruzzese, G. Arena, P. Ariola, M. Arnichand, H. Arnoux, G. Arshad, S. Ash, A. Asp, E. Asunta, O. Atanasiu, C. V. Austin, Y. Avotina, L. Axton, M. D. Ayres, C. Bachmann, C. Baciero, A. Baiao, D. Bailescu, V. Baiocchi, B. Baker, A. Baker, R. A. Balboa, I. Balden, M. Balshaw, N. Bament, R. Banks, J. W. Baranov, Y. F. Barlow, I. L. Barnard, M. A. Barnes, D. Barnsley, R. Baron Wiechec, A. Baruzzo, M. Basiuk, V. Bassan, M. Bastow, R. Batista, A. Batistoni, P. Bauer, R. Bauvir, B. Bazylev, B. Beal, J. Beaumont, P. S. Becoulet, A. Bednarczyk, P. Bekris, N. Beldishevski, M. Bell, K. Belli, F. Bellinger, M. Belo, J. K. Belo, P. Belonohy, E. Benterman, N. A. Bergsaker, H. Bernardo, J. Bernert, M. Berry, M. Bertalot, L. Beurskens, M. N. A. Bieg, B. Bielecki, J. Biewer, T. Bigi, M. Bilkova, P. Binda, F. Bizarro, J. P. S. Bjorkas, C. Blackman, K. Blackman, T. R. Blanchard, P. Blanco, E. Blatchford, P. Bobkov, V. Boboc, A. Bodnar, G. Bogar, O. Bolzonella, T. Boncagni, L. Bonham, R. Bonheure, G. Boom, J. Booth, J. Borba, D. Borodin, D. Botrugno, A. Boulbe, C. Boulting, P. Bovert, K. V. Bowden, M. Bower, C. Boyce, T. Boyer, H. J. Bradshaw, J. M. A. Braic, V. Breizman, B. Bremond, S. Brennan, P. D. Brett, A. Brezinsek, S. Bright, M. D. J. Brix, M. Broeckx, W. Brombin, M. Brown, B. C. Brown, D. P. D. Brown, M. Bruno, E. Bucalossi, J. Buch, J. Buckley, M. A. Bucko, Forschungszentrum Julich Inst Energie & Klimaforsch Plasmaphys Trilateral Euregio Cluster D-52425 Julich Germany Culham Sci Ctr CCFE Abingdon OX14 3DB Oxon England Forschungszentrum Julich Supercomp Ctr D-52425 Julich Germany Univ Milano Bicocca Piazza Sci 3 I-20126 Milan Italy Uppsala Univ Dept Phys & Astron Uppsala Sweden Aalto Univ FIN-00076 Aalto Finland BCS Barcelona Spain Culham Sci Ctr CCFE Abingdon OX14 3DB Oxon England IRFM CEA F-13108 St Paul Les Durance France Ctr Brasileiro Pesquisas Fis BR-22290180 Rio De Janeiro Brazil Consorzio CREATE I-80125 Naples Italy Consorzio RFX I-35127 Padua Italy Daegu Univ Gyongsan 712174 Gyeongbuk South Korea Univ Carlos III Madrid Dept Fis Madrid 28911 Spain Univ Ghent Dept Appl Phys B-9000 Ghent Belgium Chalmers Univ Technol Dept Earth & Space Sci SE-41296 Gothenburg Sweden Univ Cagliari Dept Elect & Elect Engn I-09123 Cagliari Italy Comenius Univ Fac Math Phys & Informat Dept Expt Phys Bratislava 84248 Slovakia Univ Strathclyde Dept Phys & Appl Phys Glasgow G4 ONG Lanark Scotland Uppsala Univ Dept Phys & Astron SE-75120 Uppsala Sweden Lund Univ Dept Phys SE-22100 Lund Sweden KTH SCI Dept Phys SE-10691 Stockholm Sweden Univ Oxford Dept Phys Oxford OX1 2JD England Univ Warwick Dept Phys Coventry CV4 7AL W Midlands England Queens Univ Dept Pure & Appl Phys Belfast BT7 1NN Antrim North Ireland Univ Catania Dipartimento Ingn Elettr Elettr & Sistemi I-95125 Catania Italy Dublin City Univ Dublin Ireland CRPP EPFL CH-1015 Lausanne Switzerland CNRS UMR 7648 Ecole Polytech F-91128 Palaiseau France EUROfus Programme Management Unit D-85748 Garching Germany Culham Sci Ctr EUROfus Programme Management Unit Abingdon OX14 3DB Oxon England European Commiss B-1049 Brussels Belgium FOM Inst DIFFER NL-3430 BE Nieuwegein Netherlands Forsch Zentrum Julich GmbH Inst Energie & Klimaforsch Plasmaphys D-52425 Julich Germany Fus Energy Joint Undertaking Barcelona 08019 Spain KTH EES Fus P

The analysis of the radiation damage of imaging systems is based on all different types-of aiialoiue/digital cameras with uncooled as well as actively cooled image sensors in the VIS/NIR/MWIR spectral ranges. The Monte Carlo N-Particle (MCNP) code has been used to determine the neutron fluence at different camera locations in JET. An explicit link between the sensor damage and the neutron fluence has been observed. Sensors show an increased dark-current and increased numbers of hot-pixels. Uncooled cameras must be replaced once per year after exposure to a neutron fluence of similar to 1.9-3.2 x 10(12)neutrons/cm(2). Such levels of fluence will be reached after approximate to 14-22 ELMy H-mode pulses during the future D-T campaign. Furthermore, dynamical noise seen as a random pattern of bright pixels was observed in the presence of hard radiation (neutrons and gammas). Failure of the digital electronics inside the cameras as well as of industrial controllers is observed beyond a neutron fluence of about similar to 4 x 10(9) neutrons/cm(2). The impact of hard radiation on the different types of electronics and possible application of cameras during future D-T campaign is discussed. (C) 2017 The Author(s). Published by Elsevier B.V.

关键词： CCd Camera Radiation damage Hot pixels Image Camera cooling

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