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Hyperglycemia in acute ischemic stroke: physiopathological and therapeutic complexity

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Neural Regeneration Research 2022年第2期17卷 292-299页

作者： federica Ferrari Antonio Moretti Roberto Federico Villa Department of Biology and Biotechnology Laboratory of Pharmacology and Molecular Medicine of Central Nervous SystemUniversity of PaviaVia FerrataPaviaItaly

Diabetes mellitus and associated chronic hyperglycemia enhance the risk of acute ischemic stroke and lead to worsened clinical outcome and increased mortality. However, post-stroke hyperglycemia is also present in a number of non-diabetic patients after acute ischemic stroke, presumably as a stress response. The aim of this review is to summarize the main effects of hyperglycemia when associated to ischemic injury in acute stroke patients, highlighting the clinical and neurological outcomes in these conditions and after the administration of the currently approved pharmacological treatment, i.e. insulin. The disappointing results of the clinical trials on insulin(including the hypoglycemic events) demand a change of strategy based on more focused therapies. Starting from the comprehensive evaluation of the physiopathological alterations occurring in the ischemic brain during hyperglycemic conditions, the effects of various classes of glucose-lowering drugs are reviewed, such as glucose-like peptide-1 receptor agonists, DPP-4 inhibitors and sodium glucose cotransporter 2 inhibitors, in the perspective of overcoming the up-to-date limitations and of evaluating the effectiveness of new potential therapeutic strategies.

关键词： acute ischemic stroke diabetes mellitus DPP-4 inhibitor glucose-like peptide-1 receptor agonist hyperglycemia hypoglycemia insulin physiopathology sodium glucose cotransporter 2 inhibitor

Exploring pre-degenerative alterations in humans using induced pluripotent stem cell-derived dopaminergic neurons

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Neural Regeneration Research 2017年第7期12卷 1068-1070页

作者： federica Bono Chiara Fiorentini Division of Pharmacology Department of Molecular andTranslational Medicine University of Brescia Brescia Italy

Understanding the cellular and molecular mechanisms underlying human neurological disorders is hindered by both the complexity of the disorders and the lack of suitable experimental models recapitulating key pathological features of the *** is a crucial issue since a limited understanding of pathogenic mechanisms precludes the development of drugs counteracting the progression of the *** neurological disorders,

关键词： in Exploring pre-degenerative alterations in humans using induced pluripotent stem cell-derived dopaminergic neurons stem DAT been that of cell PSC

Functional proteomics of adenosine triphosphatase system in the rat striatum during aging

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Neural Regeneration Research 2012年第1期7卷 6-12页

作者： Roberto Federico Villa federica Ferrari Antonella Gorini Department of Forensic Medicine and Pharmacological-Toxicological Sciences Division of Pharmacological and Toxicological Sciences Laboratory of Pharmacology and Molecular Medicine of Central Nervous System University of Pavia

The maximum rates of adenosine triphosphatase （ATPase） systems related to energy consumption were systematically evaluated in synaptic plasma membranes isolated from the striata of male Wistar rats aged 2, 6, 12, 18, and 24 months, because of their key role in presynaptic nerve ending homeostasis. The following enzyme activities were evaluated： sodium-potassium-magnesium adenosine triphosphatase （Na^＋, K^＋, Mg^2＋-ATPase）; ouabain-insensitive magnesium adenosine triphosphatase （Mg^2＋-ATPase）; sodium-potassium adenosine triphosphatase （Na^＋, K^＋-ATPase）; direct magnesium adenosine triphosphatase （Mg^2＋-ATPase）; calcium-magnesium adenosine triphosphatase （Ca^2＋, Mg^2＋-ATPase）; and acetylcholinesterase. The results showed that Na~, K＋-ATPase decreased at 18 and 24 months, Ca^2＋, Mg^2＋-ATPase and acetylcholinesterase decreased from 6 months, while Mg^2＋-ATPase was unmodified. Therefore, ATPases vary independently during aging, suggesting that the ATPase enzyme systems are of neuropathological and pharmacological importance. This could be considered as an experimental model to study regeneration processes, because of the age-dependent modifications of specific synaptic plasma membranes. ATPases cause selective changes in some cerebral functions, especially bioenergetic systems. This could be of physiopathological significance, particularly in many central nervous system diseases, where, during regenerative processes, energy availability is essential.

关键词： ATPase synaptic plasma membranes aging striatum functional proteomics

DJ-1 as a deglycating enzyme:a unique function to explain a multifaceted protein?

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Neural Regeneration Research 2017年第11期12卷 1797-1798页

作者： federica De Lazzari Marco Bisaglia Molecular Physiology and Biophysics Unit Department of BiologyUniversity of PadovaPadovaItaly

The Parkinson＇s disease （PD）-associated protein DJ-1 is considered a multifunctional protein involved in oxidative stress responses. Although a large variety of functions has been attributed to DJ- 1, currently no consensus has been found on its effective cellular activity. Indeed, the protein has been described as a transcriptional modulator, a regulator of mitochondrial activity, a stabilizer of the nuclear factor erythroid 2-related factor （Nrf2）, a chaperone, a pro- tease, and a glutathione （GSH）-independent glyoxalase （Ariga et al., 2013）. Very recently, the additional participation of the protein to carbonvl stress defense has been emereing （Richarme et al., 2015）.

关键词： DJ-1 as a deglycating enzyme multifaceted protein

*** and Exploring Lineage Data as a Service

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Data Intelligence 2022年第2期4卷 226-242页

作者： Alessandro Spinuso Malcolm Atkinson federica Magnoni Koninklijk Nederlands Meteorologisch Instituut De BiltUtrecht 3731 GAThe Netherlands University of Edinburgh EdinburghEdinburgh EH89ABUnited Kingdom Istituto Nazionale Geofisica e Vulcanologia RomeLazio 00143Italy

We present a set of configurable Web service and interactive tools,s-ProvFlow,for managing and exploiting records tracking data lineage during workflow *** facilitates detailed analysis of single *** helps users manage complex tasks by exposing the relationships between data,people,equipment and workflow runs intended to combine *** logical model extends the PROV standard to precisely record parallel data-streaming *** metadata handling encourages users to capture the application context by specifying how application attributes,often using standard vocabularies,should be *** metadata records immediately help productivity as the interactive tools support their use in selection and bulk *** rapidly appreciate the power of the encoded semantics as they reap the *** improves the quality of provenance for users and *** in turn facilitates analysis of collections of runs,enabling users to manage results and validate *** fosters reuse of data and methods and facilitates diagnostic investigations and *** present S-ProvFlow's use by scientists,research engineers and managers as part of the DARE hyper-platform as they create,validate and use their data-driven scientific workflows.

关键词： Provenance Productivity Workflows Human-in-the-loop Visualisation

Are metabolic factors still important in the era of direct antiviral agents in patients with chronic hepatitis C?

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World Journal of Gastroenterology 2013年第41期19卷 6947-6956页

作者： Alessandro Grasso federica Malfatti Roberto Testa Gastroenterology Unit Department of Internal MedicineSan Paolo Hospital

The high rate of sustained viral response(SVR)to boceprevir or telaprevir-based triple therapy in hepatitis C(HCV)-related,non-cirrhotic na ve patients or relapsers to previous antiviral treatment leads clinicians to believe that the impact of metabolic host factors on SVR is minimal when triple therapy is used,unlike what is observed with the peginterferon and ribavirin *** concept is strongly expressed by some opinion leaders on the basis of the data derived from subanalyses of registrative trials as well as from a post-hoc analysis of the phaseⅡC208 clinical *** perception of unrestrainable therapeutic success with the use of newer,more powerful antivirals is now reinforced by the brilliant results obtained with sofosbuvir,an HCV NS5B polymerase inhibitor,as well as by the data from the phaseⅡandⅢstudies on the various combinations of second-generation NS3/4A inhibitors and NS5A and/or NS5B ***,a great deal of concern has emerged from the real world scenario in which patients are often older and have more comorbidities than patients in the"world of trials".Furthermore,many of them have advanced fibrosis and previous failure with peginterferon and ribavirin *** data from the recent literature suggest that the host metabolic factors may play a minor but non-negligible role in these difficult-to-treat patients,an issue that will hopefully be investigated in further *** editorial aims to provide a detailed analysis of the role that host metabolic factors played in the past and what role they may play in the era of direct antiviral agents.

关键词： Metabolic factors Insulin resistance Direct antiviral agents Chronic hepatitis C

The Integrity of the Plant Golgi Apparatus Depends on Cell Growth-Controlled Activity of GNL1

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Molecular Plant 2013年第3期6卷 905-915页

作者： Wenyan Du Kentaro Tamura Giovanni Stefano federica Brandizzi MSU-DOE Plant Research Lab Michigan State University East Lansing MI 48824 USA Department of Plant Biology Michigan State University East Lansing MI 48824 USA Department of Botany Graduate School of Science Kyoto University Sakyo-ku Kyoto 606-8502 Japan

Membrane traffic and organelle integrity in the plant secretory pathway depend on ARF-GTPases, which are activated by guanine-nucleotide exchange factors （ARF-GEFs）. While maintenance of conserved roles, evolution of unique functions as well as tissue-specific roles have been shown for a handful of plant ARF-GEFs, a fundamental yet unanswered question concerns the extent to which their function overlaps during cell growth. To address this, we have characterized pao, a novel allele of GNOM-like 1 （GNL1）, a brefeldin A （BFA）-insensitive ARF-GEF, isolated through a confocal microscopy-based forward genetics screen of the Golgi in Arabidopsis thaliana. Specifically, we have analyzed the dependence of the integrity of trafficking routes and secretory organelles on GNL1 availability during expansion stages of cotyledon epidermal cells, an exquisite model system for vegetative cell growth analyses in intact tissues. We show that Golgi traffic is influenced largely by GNL1 availability at early stages of cotyledon cell expansion but by BFA- sensitive GEFs when cell growth terminates. These data reveal an unanticipated level of complexity in the biology of GNL1 by showing that its cellular roles are correlated with cell growth. These results also indicate that the cell growth stage is an important element weighting into functional analyses of the cellular roles of ARF-GEFs.

关键词： ARF-GEFs Golgi Arabidopsis GNL1 brefeldin A.

A useful toolbox for the detection of SCF E3 ligase activity

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Molecular Plant 2022年第11期15卷 1654-1655页

作者： federica Casagrande Qi Xie Giovanna Serino Dipartimento di Biologia e Biotecnologie“C.Darwin ”Sapienza Universitàdi RomaPiazzale Aldo Moro 500185 RomeItaly State Key Laboratory of Plant Genomics Institute of Genetics and Developmental BiologyThe Innovative Academy of Seed DesignChinese Academy of SciencesBeijing 100101China

Since its discovery about 50 years ago,the ubiquitin-proteasome system(UPS)has not stopped to surprise us for its level of sophistication and complexity in achieving substrate-specific protein degradation(Vierstra,2009).At the heart of this system lies the concerted activity of three major classes of enzymes:ubiquitin activators(E1),ubiquitin conjugators(E2),and ubiquitin ligases(or E3).E3s,together with selected E2s,are responsible for promoting the formation of a ubiquitin chain on a specific protein substrate.

关键词： stopped ligase ubiquitin

High density lipoproteins and atherosclerosis: emerging aspects

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Journal of Geriatric Cardiology 2012年第4期9卷 401-407页

作者： federica Sala Alberico Luigi Catapano Giuseppe Danilo Norata Department of Pharmacological Sciences University of Milan Via Balzaretti 9 Milan 20133 Italy IRCCSMult imedica ViaMilanese 300 Sesto San Giovanni Milan Italy Centro SISAper lo Studio dell’Aterosclerosi Ospedale Bassini Via Gorki50 Cinisello Bal samo Italy The Blizard Institute Barts and the LondonSchool of Medicine & Dentistry Queen Mary University Turner Street London E1 2AD UK

High density lipoproteins (HDL) promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion. This ability is responsible for the most relevant anti-atherogenic effect of HDL. The ability of HDL to promote cholesterol efflux results also in the modulation of a series of responses in the immune cells involved in atherosclerosis,includingmonocyte-macrophages, B and T ***, during inflammation, the composition of this class of lipoproteins varies to a large extent, thus promoting the formation of dysfunctional HDL. The aim of this review is to discuss the emerging role of HDL in modulating the activity of immune cells and immune-inflammatory mediators during atherogenesis.

关键词： Apolipoprotein High density lipoproteins Immune response Sphingosine-1-phosphate