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BIOCELL 2023年第7期47卷 1499-1508页

作者： GIULIA CHIABOTTO stefania bruno Department of Medical Sciences University of TorinoTorino10126Italy Molecular Biotechnology Center University of TorinoTorino10126Italy

Renal fibrosis and inflammation are common pathological features of chronic kidney disease(CKD).Since currently available treatments can only delay the progression of CKD,the outcome of patients with CKD is still *** therapeutic option for the prevention of CKD-related complications could be the use of mesenchymal stromal cells(MSCs),which have shown beneficial effects in tissue fibrosis and regeneration after ***,safety issues,such as cellular rejection and carcinogenicity,limit their clinical *** the bioactive factors secreted by MSCs,extracellular vesicles(EVs)have shown the same beneficial effect of MSCs,without any notable side *** heterogeneous population of membranous nano-sized particles can deliver genetic material and functional proteins to injured cells,prompting tissue *** we describe the anti-fibrotic and antiinflammatory properties of MSC-derived EVs in CKD preclinical models and summarize the potential molecular mechanisms involved in the regulation of renal fibrosis and inflammation.

关键词： Chronic kidney disease Renal fibrosis Epithelial-to-mesenchymal transition Mesenchymal stromal cell Extracellular vesicles

Initial failures of anti-tau antibodies in Alzheimer’s disease are reminiscent of the amyloid-βstory

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Neural Regeneration Research 2023年第1期18卷 117-118页

作者： bruno P.Imbimbo Claudia Balducci stefania Ippati Mark Watling Department of Research&Development Chiesi FarmaceuticiParmaItaly Department of Neuroscience Istituto di Ricerche Farmacologiche“Mario Negri”IRCCSMilanItaly San Raffaele Scientific Institute San Raffaele HospitalMilanItaly CNS&Pain Department TranScrip Ltd.ReadingUK

Tau is an important protein of the central nervous system formed by 352-441 amino acids and encoded by the MAPT(microtubule-associated protein tau)gene on chromosome 17 which generates 6 *** is located in axons,dendrites,nucleus,cell membrane,and synapses of *** protein is also expressed to a lesser extent in astrocytes and oligodendrocytes,although its role in these cells has been little *** protein is also present in the interstitial fluid and can cross into the cerebrospinal fluid(CSF)and reach the systemic circulation.

关键词： tau Alzheimer cerebrospinal

Unique immunological profile in patients with COVID-19

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Cellular & Molecular Immunology 2021年第3期18卷 604-612页

作者： stefania Varchetta Dalila Mele Barbara Olivier stefania Mantovani Serena Ludovisi Antonella Cerino Raffaele bruno Alberto Castelli Mario Mosconi Marco Vecchia Silvia Roda Michele Sachs Catherine Klersy Mario U.Mondelli Division of Infectious Diseases Ⅱ and Immunology Fondazione IRCCS Polidinico San MatteoPaviaItaly Department of Internal Medicine and Therapeutics University of PaviaPaviaItaly Division of Infectious Diseases I Fondazione IRCCS Polidinico San MatteoPaviaItaly Department of Clinical SurgicalDiagnosticand Pediatric SciencesUniversity of PaviaPaviaItaly Division of Orthopaedics and Traumatology Fondazione IRCCS Polidinico San MatteoPaviaItaly Department of Clinical-Surgical Diagnostic and Pediatric SciencesUniversity of PaviaPaviaItaly Clinical Epidemiology&Biometry Unit IRCCS Fondazione Polidinico San MatteoPaviaItaly

The relationship between severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)and host immunity is poorly *** performed an extensive analysis of immune responses in 32 patients with severe COVID-19,some of whom succumbed A control population of healthy subjects was *** with COVID-19 had an altered distribution of peripheral blood lymphocytes,with an increased proportion of mature natural killer(NK)cells and low T-cell *** cells and CD8^(+)T cells overexpressed T-cellimmunoglobulin and mucin domain-3(TIM-3)and *** cell exhaustion was attested by increased frequencies of programmed cell death protein 1(PD-1)positive cells and reduced frequencies of natural killer group 2 member D(NKG2D)-,DNAX accessory molecule-1(DNAM-1)-and sialic acid-binding Ig-like lectin 7(Siglec-7)-expressing NK cells,associated with a reduced ability to secrete interferon(IFN)γ.Patients with poor outcome showed a contraction of immature CD56^(bright) and an expansion of mature CD57^(+)F_(CEI)Rlγ^(eng) adaptive NK cells compared to *** serum levels of IL-6 were also more frequently identified in deceased patients compared to *** note,monocytes secreted abundant quantities of IL-6,IL-8,and IL-1β which persisted at lower levels several weeks after recovery with concomitant normalization of CD69,PD-1 and TIM-3 expression and restoration of CD8^(+)T cell numbers.A hyperactivated/exhausted immune response dominate in severe SARS-CoV-2 infection,probably driven by an uncontrolled secretion of inflammatory cytokines by *** findings unveil a unique immunological profile in COVID-19 patients that will help to design effective stage-specific treatments for this potentially deadly disease.

关键词： C0VID-19 NK cells TIM-3 IL6 Monocytes

Chitosan tubes enriched with fresh skeletal muscle fibers for delayed repair of peripheral nerve defects

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Neural Regeneration Research 2019年第6期14卷 1079-1084页

作者： AlessANDro Crosio Benedetta Elena Fornasari Giovanna Gambarotta Stefano Geuna stefania Raimondo bruno Battiston Pierluigi Tos Giulia Ronchi Department of Orthopedics and Traumatology II-Surgery for Hand and Upper Limb-AOU Città della Salute e della Scienza di Torino-CTO Hospital Department of Clinical and Biological Sciences University of Torino Neuroscience Institute Cavalieri Ottolenghi University of Torino UO Microchirurgia e Chirurgia della Mano Ospedale Gaetano Pini

Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal stump of chronically transected nerves; moreover, Schwann cells undergo atrophy, losing their ability to sustain regeneration. In the present study, to provide a three-dimensional environment and trophic factors supporting Schwann cell activity and axon re-growth, we combined the use of an effective conduit(a chitosan tube) with a promising intraluminal structure(fresh longitudinal skeletal muscle fibers). This enriched conduit was used to repair a 10-mm rat median nerve gap after 3-month delay and functional and morphometrical analyses were performed 4 months after nerve reconstruction. Our data show that the enriched chitosan conduit is as effective as the hollow chitosan conduit in promoting nerve regeneration,and its efficacy is not statistically different from the autograft, considered the "gold standard" technique for nerve reconstruction. Since hollow tubes not always lead to good results after long defects(> 20 mm), we believe that the conduit enriched with fresh muscle fibers could be a promising strategy to repair longer gaps, as muscle fibers create a favorable three-dimensional environment and release trophic factors. All procedures were approved by the Bioethical Committee of the University of Torino and by the Italian Ministry of Health(approval number: 864/2016/PR) on September 14, 2016.

关键词： tubulization Schwann cells scaffold tissue engineering nerve reconstruction morphometrical analyses grasping test secondary repair median nerve nerve regeneration

Opportunities and challenges of implementing Pharmacogenomics in cancer drug development

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Cancer Drug Resistance 2019年第1期2卷 43-52页

作者： Paolo Tarantino Dario Trapani stefania Morganti Emanuela Ferraro Giulia Viale Paolo D’Amico bruno Achutti Duso Giuseppe Curigliano Division of Early Drug Development for Innovative Therapies IEOEuropean Institute of Oncology IRCCSMilan 20141Italy Department of Oncology and Haematology(DIPO) University of MilanMilan 20122Italy

Cancer drug development is a time and resources consuming *** 90%of drugs entering clinical trials fail due to lack of efficacy and/or safety issues,more often after conspicuous research and economic *** of the discarded drugs might be beneficial only in a subgroup of the study patients,and some adverse events might be prevented by identifying those patients more vulnerable to *** implementation of pharmacogenomic biomarkers allows the categorization of patients,to predict efficacy and toxicity and to optimize the drug development *** seventy FDA approved drugs currently present one or more genetic biomarker to keep in consideration,and with the progress of Precision Medicine tailoring therapies on individuals’genomic landscape promises to become a new standard of cancer *** the current article we review the role of pharmacogenomics in cancer drug development,underlying the advantages and challenges of their implementation.

关键词： Pharmacogenomics cancer drug development precision medicine clinical trials

Genomic and genetic alterations influence the progression of gastric cancer

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World Journal of Gastroenterology 2011年第3期17卷 290-299页

作者： stefania Nobili Lorenzo bruno Ida Landini Cristina Napoli Paolo Bechi Francesco Tonelli Carlos A Rubio Enrico Mini Gabriella Nesi Department of Preclinical and Clinical Pharmacology University of Florence Department of Critical Care Medicine and Surgery University of Florence Department of Clinical Physiopathology University of Florence Department of Pathology Karolinska Institute and University Hospital Division of Pathological Anatomy Department of Critical Care Medicine and SurgeryUniversity of Florence

Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric *** this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.

关键词： Gastric cancer Gene alterations Prognosis Molecular pathology

Magnetic resonance imaging differential diagnosis of brainstem lesions in children

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World Journal of Radiology 2016年第1期8卷 1-20页

作者： Carlo Cosimo Quattrocchi Yuri Errante Maria Camilla Rossi Espagnet stefania Galassi Sabino Walter Della Sala bruno Bernardi Giuseppe Fariello Daniela Longo Department of Medicine and Surgery Università Campus Bio-Medico di Roma Department of NESMOS Sant’ Andrea HospitalUniversità La Sapienza Unit of Neuroradiology Bambino Gesù Children’s Research Hospital IRCCS Fatebenefratelli S. Pietro Hospital

Differential diagnosis of brainstem lesions,either isolated or in association with cerebellar and supra-tentorial lesions,can be challenging. Knowledge of the structural organization is crucial for the differential diagnosis and establishment of prognosis of pathologies with involvement of the brainstem. Familiarity with the location of the lesions in the brainstem is essential,especially in the pediatric population. Magnetic resonance imaging(MRI) is the most sensitive and specific imaging technique for diagnosing disorders of the posterior fossa and,particularly,the brainstem. High magnetic static field MRI allows detailed visualization of the morphology,signal intensity and metabolic content of the brainstem nuclei,together with visualization of the normal development and myelination. In this pictorial essay we review the brainstem pathology in pediatric patients and consider the MR imaging patterns that may help the radiologist to differentiate among vascular,toxico-metabolic,infectiveinflammatory,degenerative and neoplastic processes. Helpful MR tips can guide the differential diagnosis: These include the location and morphology of lesions,the brainstem vascularization territories,gray and white matter distribution and tissue selective vulnerability.

关键词： Brainstem Pediatrics Differential diagnosis Neuroradiology Magnetic resonance