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Advancing immunosuppression in liver transplantation: A narrative review

Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 441-448页

作者： Samuele Iesari francesca laura nava Ilaria Elena Zais Laurent Coubeau Mariano Ferraresso Evaldo Favi Jan Lerut General Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico15 Via della Commenda20122 MilanItaly Institut de Recherche Expérimentale et Clinique Universitécatholique de Louvain10 Avenue Hippocrate1200 BrusselsBelgium Service de Chirurgie et Transplantation Abdominale Cliniques Universitaires Saint-Luc55 Avenue Hippocrate1200 BrusselsBelgium Department of Clinical Sciences and Community Health Universitàdegli Studi di Milano19 Via della Commenda20122 MilanItaly

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation(LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solidorgan transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

关键词： Liver transplantation Immunosuppression Drug development Long-term results Clinical operational tolerance

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Is it possible to develop a cerebellar reserve?

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Neural Regeneration Research 2022年第5期17卷 994-996页

作者： francesca Gelfo laura Petrosini Department of Human Sciences Guglielmo Marconi UniversityRomeItaly IRCCS Fondazione Santa Lucia RomeItaly

The concept of neural plasticity accounts for the now well clarified brain ability to react to internal and external stimuli by transforming its structure and *** translation of whatever experience in specific electrical signals that run through our neural networks induces a number of plastic changes at both functional and structural levels.

关键词： function. translation clarified

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What good is the reserve? A translational perspective for the managing of cognitive decline

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Neural Regeneration Research 2019年第7期14卷 1219-1220页

作者： laura Serra francesca Gelfo Neuroimaging Laboratory IRCCS Fondazione Santa Lucia Department of Clinical and Behavioural Neurology IRCCS Fondazione Santa Lucia Department of Human Sciences Guglielmo Marconi University

The concept of reserve appears in the neurological literature in the 1940s arising from the observation that there is no linear relationship between neurological damage and severity of the clinical ***,this concept sustains that the experiences pursued during life-span enrich the brain by making it more resilient to neuronal ***,in the last three decades the reserve concept has become very popular in the scientific field,mainly associated with the pathophysiological mechanisms underlying the Alzheimer’s Disease(AD)(Serra et al.,2018;Stern et al.,2018).

关键词： reserve appears neurological literature reserve concept

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Behavioral plasticity, behavioral syndromes and animal personality in crustacean decapods： An imperfect map is better than no map

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Current Zoology 2012年第4期58卷 567-579页

作者： francesca GHERARDI laura AQUILONI Elena TRICARICO Dipartimento di Biologia Evoluzionistica 'Leo Pardi' Universith degli Studi di Firenze Via Romana 17 50125 Firenze Italy

Despite their key role as model organisms in many behavioral studies, crustacean decapods have been only slightly touched upon by the recent surge of scientific interest in animal personality. Only seven articles investigated the issue in a handful of species among hermit crabs, crabs, and crayfish. Obviously, a limited number of publications does not mean that personality is rare in decapods. On the contrary, few studies might be the result of a form of reluctance by behavioral ecologists to deal with such a phenomenon in these and other invertebrates. This reluctance contrasts with the enthusiasm shown in tackling the beha- vioral plasticity issue. Here we discuss the possible theoretical and methodological difficulties raised by applying the animal per-sonality perspective to decapods and analyze implications of personality studies for their ecology, conservation, and welfare. By highlighting gaps in knowledge and directions of future research, our intention is to increase scientific emphasis on the issue.

关键词： Crustacean decapods Behavioral plasticity Animal personality Behavioral syndromes Conservation Animal welfare

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Relationship between MRI pertusion and clinical severity in multiple sclerosis

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Neural Regeneration Research 2020年第4期15卷 646-652页

作者： Maria Marcella Laganà laura Pelizzari francesca Baglio IRCCS Fondazione Don Carlo Gnocchi

Perfusion alterations within several brain regions have been shown in multiple sclerosis patients using different magnetic resonance imaging(MRI)***,MRI-derived brain perfusion metrics have been investigated in association with multiple sclerosis phenotypes,physical disability,and cognitive ***,a review focused on these aspects is still *** aim was to review all the studies investigating the relationship between perfusion MRI and clinical severity during the last fifteen years to understand the clinical relevance of these *** differences among phenotypes were observed both with 1.5T and 3T scanners,with progressive multiple sclerosis presenting with lower perfusion values than relapsing-remitting multiple sclerosis ***,only 3T scanners showed a statistically significant *** results about the association between MRI-derived perfusion metrics and physical disability scores were ***,the majority of the studies showed that lower brain perfusion and longer transit time are associated with more severe physical disability and worse cognitive performances.

关键词： brain perfusion cerebral blood flow cognition disability magnetic resonance imaging MRI multiple sclerosis phenotypes progressive relapsing remitting

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Fekete-Gauss Spectral Elements for Incompressible Navier-Stokes Flows:The Two-Dimensional Case

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Communications in Computational Physics 2013年第5期13卷 1309-1329页

作者： laura Lazar Richard Pasquetti francesca Rapetti Lab.J.A.Dieudonne UMR 7351 CNRS UNSUniversite de Nice-Sophia Antipolis06108 Nice Cedex 02France

Spectral element methods on simplicial meshes,say TSEM,show both the advantages of spectral and finite element methods,i.e.,spectral accuracy and geometrical *** present a TSEM solver of the two-dimensional(2D)incompressible Navier-Stokes equations,with possible extension to the 3D *** uses a projection method in time and piecewise polynomial basis functions of arbitrary degree in *** so-called Fekete-Gauss TSEM is employed,i.e.,Fekete(***)points of the triangle are used as interpolation(***)*** the sake of consistency,isoparametric elements are used to approximate curved *** resolution algorithm is based on an efficient Schur complement method,so that one only solves for the element boundary ***,the algebraic system is never assembled,therefore the number of degrees of freedom is not *** accuracy study is carried out and results are provided for classical benchmarks:the driven cavity flow,the flow between eccentric cylinders and the flow past a cylinder.

关键词： Spectral elements simplicial meshes Fekete-Gauss approximation Navier-Stokes equations projection methods domain decomposition

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New obesity classification criteria as a tool for bariatricsurgery indication

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World Journal of Gastroenterology 2016年第2期22卷 681-703页

作者： Antonino De Lorenzo laura Soldati francesca Sarlo Menotti Calvani Nicola Di Lorenzo laura Di Renzo Division of Clinical Nutrition and Nutrigenomic Department of Biomedicine and PreventionUniversity of Tor Vergata00133 RomeItaly Department of Internal Medicine UOSD Service of Clinical Nutritionparenteral therapy and anorexia nervosaPoliclinico Tor Vergata00133 RomeItaly Department of Health Sciences University of Milan20122 MilanItaly Department of Agriculture University of Naples“Federico II” 80055 Portici(NA)Italy Department of Surgical Sciences University of Tor VergataPoliclinico Tor Vergata00133 RomeItaly

Obesity plays relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional, and metabolic factors. Due to the role of adipose tissue in lipid and glucose metabolism, and low grade inflammation, it is necessary to classify obesity on the basis of body fat composition and distribution, rather than the simply increase of body weight, and the Body Mass Index. The new term of adiposopathy(‘‘sick fat'') clearly defines the pathogenic role of adipose tissue. Four phenotypes of obese individuals have been described:(1) normal weight obese(NWO);(2) metabolically obese normal weight;(3) metabolically healthy obese; and(4) metabolically unhealthy obese or "at risk" obese. Moreover, sarcopenic obesity has been related to all the phenotypes. The category of normal weight lean, represented by metabolically healthy normal weight has been classified to distinguish from NWO. It is crucial to recommend a bariatric surgery taking into account adiposopathy and sick fat that occurs with the expansion of fat mass, changing the inflammatory and metabolic profile of the patient. Body fat percentage and genetic polymorphism have to be evaluated to personalize the best bariatric surgery intervention.

关键词： Obesity Adiposopathy Normal weightlean Normal weight obese Metabolically obese normalweight Metabolically healthy obese Metabolicallyhealthy normal weight Metabolically unhealthy obese Laparoscopic gastric banding Fat mass

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Sperm quality improvement after natural anti-oxidant treatment of asthenoteratospermic men with leukocytospermia

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Asian Journal of Andrology 2008年第2期10卷 201-206页

作者： Paola Piomboni laura Gambera francesca Serafini Giovanna Campanella Giuseppe Morgante Vincenzo De Leo Department of Surgery Biology SectionObstetrics and Reproductive Medicine Gynecology and Obstetrics Section University of Siena Siena 53100 Italy Center for Diagnosis and Treatment of Couple Sterility Siena Hospital Siena 53100 Italy Department of Pediatrics Obstetrics and Reproductive Medicine Gynecology and Obstetrics Section University of Siena Siena 53100 Italy

Aim： To study the immune-modulating and anti-oxidant effects of beta-glucan, papaya, lactoferrin, and vitamins C and E on sperm characteristics of patients with asthenoteratozoospermia associated with leucocytosis. Methods： Fifty-one patients referred to our Sterility Center for semen analysis were selected. Sperm parameters were assessed before and after patient＇s treatment with beta-glucan, lactoferrin, papaya, and vitamins C and E. DNA damage was assessed by the acridine orange test and sperm structural characteristics were evaluated by transmission electron microscopy. Results： After 90 days of treatment, an increase in the percentage of morphologically normal sperm （17.0 ± 5.2 vs. 29.8 ± 6.5） and total progressive motility （19.0± 7.8 vs. 34.8 ± 6.8） were detected. Structural sperm characteristics as well as chromatin integrity were also improved after treatment. In terms of leukocyte concentration in seminal fluid, a significant reduction was recorded （2.2 ± 0.9 vs. 0.9± 0.2）. Conclusion： The treatment of an inflammatory process by the synergic action of immune modulators and anti-oxidants could protect sperm during maturation and migration, leading to improved sperm function. （Asian JAndrol 2008 Mar;. 10： 201-206）

关键词： asthenoteratozoospermia leukocytospermia anti-oxidant beta-glucan papaya lactoferrin vitamin C vitamin E chromatinintegrity transmission electron microscopy

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Proteomic insights on the metabolism in inflammatory bowel disease

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World Journal of Gastroenterology 2020年第7期26卷 696-705页

作者： laura francesca Pisani Manuela Moriggi Cecilia Gelfi Maurizio Vecchi Luca Pastorelli Gastroenterology and Digestive Endoscopy Unit IRCCS Policlinico San DonatoSan Donato Milanese 20097Italy Department of Biomedical Science for Health University of the Study of MilanIRCCS Istituto Ortopedico GaleazziMilan 20122Italy Gastroenterology and Endoscopy Unit IRCCS Ca'Granda FoundationPoliclinico HospitalUniversity of the Study of MilanMilan 20122Italy Department of Biomedical Science for Health University of the Study of MilanMilan 20122Italy

Inflammatory bowel diseases(IBD)are chronic and relapsing inflammatory conditions of the gut that include Crohn's disease and ulcerative *** pathogenesis of IBD is not completely unraveled,IBD are multi-factorial diseases with reported alterations in the gut microbiota,activation of different immune cell types,changes in the vascular endothelium,and alterations in the tight junctions’structure of the colonic epithelial *** represents a useful tool to enhance our biological understanding and to discover biomarkers in blood and intestinal *** is expected to provide reproducible and quantitative data that can support clinical assessments and help clinicians in the diagnosis and treatment of *** a differential diagnosis of Crohn's disease and ulcerative colitis and the prediction of treatment response can be deducted by finding meaningful *** some non-invasive biomarkers have been described,none can be considered as the“gold standard”for IBD diagnosis,disease activity and therapy *** these reason new studies have proposed an“IBD signature”,which consists in a panel of biomarkers used to assess *** above described approach characterizes“omics”and in this review we will focus on proteomics.

关键词： Proteomics Inflammatory bowel disease Cronh’s disease Ulcerative colitis Proteins Biomarkers discovery

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Chemokine and chemotactic signals in dendritic cell migration

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Cellular & Molecular Immunology 2018年第4期15卷 346-352页

作者： laura Tiberio Annalisa Del Prete Tiziana Schioppa francesca Sozio Daniela Bosisio Silvano Sozzani Department of Molecular and Translational Medicine University of BresciaBresciaItaly Humanitas Clinical and Research Institute Rozzano-MilanoItaly

Dendritic cells (DCs) are professional antigen-presenting cells responsible for the activation of specific T-cell responses and for thedevelopment of immune tolerance. Immature DCs reside in peripheral tissues and specialize in antigen capture, whereas matureDCs reside mostly in the secondary lymphoid organs where they act as antigen-presenting cells. The correct localization of DCs isstrictly regulated by a large variety of chemotactic and nonchemotactic signals that include bacterial products, DAMPs (dangerassociated molecular patterns), complement proteins, lipids, and chemokines. These signals function both individually and inconcert, generating a complex regulatory network. This network is regulated at multiple levels through different strategies, such assynergistic interactions, proteolytic processing, and the actions of atypical chemokine receptors. Understanding this complexscenario will help to clarify the role of DCs in different pathological conditions, such as autoimmune diseases and cancers and willuncover new molecular targets for therapeutic interventions.

关键词： generating network mostly

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