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Metabolic regulation of microglial phagocytosis:Implications for Alzheimer’s disease therapeutics

Translational Neurodegeneration 2023年第1期12卷 205-224页

作者： Izabela Lepiarz-Raba Ismail Gbadamosi Roberta Florea rosa chiara paolicelli Ali Jawaid Laboratory for Translational Research in Neuropsychiatric Disorders(TREND) BRAINCITY:Center of Excellence for Neural Plasticity and Brain DisordersNencki Institute of Experimental BiologyWarsawPoland Swiss Federal Institute of Technology(ETH) ZurichSwitzerland Department of Biomedical Sciences University of LausanneLausanneSwitzerland

Microglia,the resident immune cells of the brain,are increasingly implicated in the regulation of brain health and *** perform multiple functions in the central nervous system,including surveillance,phagocytosis and release of a variety of soluble ***,a majority of their functions are closely related to changes in their *** natural inter-dependency between core microglial properties and metabolism offers a unique opportunity to modulate microglial activities via nutritional or metabolic *** this review,we examine the existing scientific literature to synthesize the hypothesis that microglial phagocytosis of amyloid beta(Aβ)aggregates in Alzheimer’s disease(AD)can be selectively enhanced via metabolic *** first review the basics of microglial metabolism and the effects of common metabolites,such as glucose,lipids,ketone bodies,glutamine,pyruvate and lactate,on microglial inflammatory and phagocytic ***,we examine the evidence for dysregulation of microglial metabolism in *** is followed by a review of in vivo studies on metabolic manipulation of microglial functions to ascertain their therapeutic potential in ***,we discuss the effects of metabolic factors on microglial phagocytosis of healthy synapses,a pathological process that also contributes to the progression of *** conclude by enlisting the current challenges that need to be addressed before strategies to harness microglial phagocytosis to clear pathological protein deposits in AD and other neurodegenerative disorders can be widely adopted.

关键词： Microglia Metabolism Alzheimer’s disease Neurodegeneration Inflammation Phagocytosis

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Searching for alternatives to brain regeneration

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Neural Regeneration Research 2021年第11期16卷 2198-2200页

作者： chiara La rosa Luca Bonfanti Neuroscience Institute Cavalieri Ottolenghi(NICO) OrbassanoItaly Department of Veterinary Sciences University of TurinGrugliascoItaly

Brain regeneration from an evolutionary perspective:Brain regeneration(the full restoration of tissue after loss from injury or disease)is the most sought after goal for researchers working in developmental *** also appears to be the most challenging to achieve when considering the mammalian *** remarkable regenerative capacities can be present in the central nervous systems of many non-mammalian vertebrates(e.g.,fish,amphibians),these kinds of processes appear to be dramatically reduced in mammals(Bonfanti,2011).

关键词： regeneration sought injury

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Lower Continental Crusts Involved in the Alpine Orogeny:New Insight from the Santa Lucia Nappe Metasediments(Corsica,France)

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Acta Geologica Sinica(English Edition) 2024年第4期98卷 904-920页

作者： chiara FRASSI Maria DI rosa Luca PANDOLFI Michele MARRONI Dipartimento di Scienze della Terra Universitàdi PisaVia Santa Maria 5356126 PisaItaly Istituto di Geoscienze e Georisorse IGG-CNRVia Moruzzi50124 PisaItaly

In the Alpine Corsica(France),the Santa Lucia Nappe represents a peculiar unit preserving the unique relicts of Paleozoic lower to medium continental *** consists of composite basement affected by Permian granulite facies metamorphic conditions unconformably covered by a Late Cretaceous clastic sequence(Tomboni Conglomerate and Tralonca Flysch)affected by polyphase deformation and *** this work,we present a new reconstruction of the deformation events registered by the Tralonca Flysch during the Alpine *** D1 phase was testified by rare isoclinal *** D2 phase produced a continuous foliation and a map-scale sheath-fold with a top-to-W sense of *** D3 phase produced E-verging non-cylindrical folds and S3 crenulation cleavage that is not associated to metamorphic *** present the first temperature-pressure-deformation(P-T-d)path for the Tralonca Flysch,demonstrating that the Santa Lucia Nappe underwent accretion and then first stage exhumation in the Alpine wedge during the D1 phase with pressure and temperature peaks both occurred under blueschist metamorphic *** D2 phase occurred at lower pressure-temperature conditions during a second stage *** pressure-temperaturedeformation path is comparable with those of the Lower Units(i.e.,the subducted continental units of Alpine Corsica)suggesting a common geodynamic history.

关键词： blueschist-facies metamorphism P-T-d path Santa Lucia Nappe Corsica Alpine orogeny

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Do large brains of long-living mammals prefer non-newly generated,immature neurons？

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Neural Regeneration Research 2018年第4期13卷 633-634页

作者： Ottavia Palazzo chiara La rosa Matteo Piumatti Luca Bonfanti Neuroscience Institute Cavalieri Ottolenghi(NICO) OrbassanoItaly institute of zoology-neurogenetics universitat regensburgGermany department of veterinary sciences university of turinGrugliasco(TO)Italy universitélibre de bruxelles(ulb) institute for interdisciplinary research in human biology(iribhm)BrusselsBelgium

Brain plasticity is heterogeneous in mammals：Brain regeneration and repair are the dream of every neurobiologist as well as every common citizen in the world who knows that most neurological diseases,dementia and other age-related problems affecting the central nervous system（CNS）do represent a heavy health and social *** re-generative processes are not＂ a natural property of the mammalian CNS, rather, due to evolutionary constraints they seem substantially reduced （if compared to those occurring in non-mammalian vertebrates） and hardly inducible by therapeutic approaches （reviewed in Martino et al., 2011）.

关键词： PSA Figure DCX Do large brains of long-living mammals prefer non-newly generated,immature neurons

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Epidemiology and clinical features of cystic hydatidosis in Western Sicily:A ten-year review

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World Journal of Gastroenterology 2013年第48期19卷 9351-9358页

作者： Elisa Cappello Bruno Cacopardo Eleonora Caltabiano Sigismindo Li Volsi rosa chiara Mauro Sapienza Luciano Nigro Department of Clinical and Molecular Biomedicine Chair of Infectious Diseases University of Catania 95124 Catania Italy Unit of Infectious Diseases "Basilotta" Hospital 95014 Nicosia Italy

AIM:To assess retrospectively the epidemiological and clinical aspects of cystic echinococcosis(CE)and to evaluate follow-up and response to treatment in patients affected by ***:From January 2000 to December 2010,all patients affected by CE at the Infectious Diseases Units of the University of Catania and of Basilotta Hospital in Nicosia-Enna,were enrolled as participants in the ***,clinical and laboratory data were collected for each *** of CE was performed using clinical imaging and laboratory *** to treatment was categorized as follows:"cure"as the disappearance or complete calcification of cyst/s;"improvement"as a reduction in the diameter and/or number of existing cysts;and"impairment"as an increase in the diameter and/or number of existing cyst/s and the onset of relapses(i.e.,the onset of new cyst/s and an increase in the diameter of previously existing cyst/s and/or *** E(IgE)titers and eosinophil percentages were evaluated at diagnosis,at six months after the initiation of treatment and again in the case of ***-eosinophilia was defined as an eosinophil percentage of≥6%.RESULTS:Thirty-two patients were diagnosed with CE in our Unit during the research period,with a malefemale ratio of 2:*** the time of diagnosis,40%of patients presented a single CE *** percent showed multi-organ *** liver-lung localization ratio was 2:*** below the age of 50 at diagnosis were more likely to have multiple cysts(73.7%vs 35.5%,P<0.05).Regarding treatment,30 patients were treated medically and 16 *** patients were treated both medically and *** were seen to be less frequent in patients treated with albendazole before and after *** cure or an improvement was achieved in 23 *** was observed in one *** patients showed no *** were more frequent in those patients treated before 2005.

关键词： Cystic echinococcosis Hydatid disease Cestode infections Epidemiology Diagnosis

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Two rare cases of benign hyperlipasemia in children

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World Journal of Clinical Cases 2014年第1期2卷 16-19页

作者： Elena Lionetti Ruggiero Francavilla Salvatore Leonardi Stefania Tomarchio Alessia Gennaro chiara Franzonello Mario La rosa Department of Medical and Pediatric Science University of Catania 95123 Catania Italy Department of Paediatrics University of Bari 70100 Bari Italy

Gullo's syndrome is a newly identified condition characterized by a chronic elevation of pancreatic amylase and/or lipase in the absence of pancreatic disease. Until now, only one case of benign isolated hyperlipasemia in children has been recorded. We describe two children with benign and not familial increase of serum lipase. Case 1: a six year old girl presented with occasional discovery of serum lipase elevation. Medical history was silent for pancreatic hyperenzymemia. The screening for possible causes for elevated lipase(genetic, autoimmune and infectious diseases) was normal. The serum lipase increased three fold over the upper limit(193 U/L; reference range 0-60 U/L), with daily fluctuation of values. Both ultrasound scan and magnetic resonance imaging were normal. The genetic mutation associated with chronic pancreatitis was negative. We followed up this patient for two years with blood tests every six months and she did not show any signs or symptoms of pancreatic disease, except for the high level of lipase serum. Case 2: an eight year old girl complained of nausea, vomiting and severe abdominal pain in theepigastric region after eating for the last two weeks. Full blood count, electrolytes, C-reactive protein, liver and renal function were normal. Serum lipase was 96 U/L(reference range 0-60 U/L). The screening for the possible causes of pancreatic disease was negative. Endoscopy of the upper gastrointestinal tract, ultrasound, computed tomography scan and magnetic resonance imaging were normal. One year after the presentation of the symptoms, the patient became asymptomatic although the level of serum lipase continued to be high.

关键词： Amylase Lipase Pancreatic hyperenzymemia Gullo’s syndrome Benign hyperlipasemia

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Solid lipid nanoparticles delivering anti-inflammatory drugs to treat inflammatory bowel disease: Effects in an in vivo model

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World Journal of Gastroenterology 2017年第23期23卷 4200-4210页

作者： chiara Dianzani Federica Foglietta Benedetta Ferrara Arianna Carolina rosa Elisabetta Muntoni Paolo Gasco Carlo Della Pepa Roberto Canaparo Loredana Serpe Department of Drug Science and Technology University of Torino Nanovector s.r.l

To improve anti-inflammatory activity while reducing drug doses, we developed a nanoformulation carrying dexamethasone and *** cholesteryl butyrate-solid lipid nanoparticles (DxCb-SLN) were obtained with the warm microemulsion method. The anti-inflammatory activity of this novel nanoformulation has been investigated in vitro (cell adhesion to human vascular endothelial cells and pro-inflammatory cytokine release by lipopolysaccharide-induced polymorphonuclear cells) and in vivo (disease activity index and cytokine plasma concentrations in a dextran sulfate sodium-induced mouse colitis) models. Each drug was also administered separately to compare its effects with those induced by their co-administration in SLN at the same ***-SLN at the lowest concentration tested (Dx 2.5 nmol/L and Cb 0.1 μmol/L) were able to exert a more than additive effect compared to the sum of the individual effects of each drug, inducing a significant in vitro inhibition of cell adhesion and a significant decrease of pro-inflammatory cytokine (IL-1β and TNF-α) in both in vitro and in vivo models. Notably, only the DxCb nanoformulation administration was able to achieve a significant cytokine decrease compared to the cytokine plasma concentration of the untreated mice with dextran sulfate sodium-induced colitis. Specifically, DxCb-SLN induced a IL-1β plasma concentration of 61.77% ± 3.19%, whereas Dx or Cb used separately induced a concentration of 90.0% ± 2.8% and 91.40% ± 7.5%, respectively; DxCb-SLN induced a TNF-α plasma concentration of 30.8% ± 8.9%, whereas Dx or Cb used separately induced ones of 99.5% ± 4.9% and 71.1% ± 10.9%, *** results indicate that the co-administration of dexamethasone and butyrate by nanoparticles may be beneficial for inflammatory bowel disease treatment.

关键词： Nanoparticles Dexamethasone Butyrate Inflammatory bowel disease Drug delivery systems

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Trichoderma harzianum enhances tomato indirect defense against aphids

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Insect Science 2017年第6期24卷 1025-1033页

作者： Mariangela Coppola Pasquale Cascone Maria Luisa Chiusano chiara Colantuono Matteo Lorito Francesco Pennacchio rosa Rao Sheridan Lois Woo Emilio Guerrieri Maria Cristina Digilio Department of Agricultural Sciences University of Naples Federico II Portici Italy CNR--IPSP Portici Italy

Many fungal root symbionts of the genus Trichoderma are well-known for their beneficial effects on agronomic performance and protection against plant pathogens; moreover, they may enhance protection from insect pests, by triggering plant resistance mechanisms. Defense barriers against insects are induced by the activation of metabolic pathways involved in the production of defense-related plant compounds, either directly active against herbivore insects, or exerting an indirect effect, by increasing the attrac- tion of herbivore natural enemies. In a model system composed of the tomato plant, the aphid Macrosiphum euphorbiae and the parasitoid Aphidius ervi, plant metabolic changes induced by Trichoderma harzianum and their effects on higher trophic levels have been assessed. T. harzianum T22 treatments induce a primed state that upon aphid attacks leads to an increased attraction of aphid parasitoids, mediated by the enhanced produc- tion of volatile organic compounds （VOCs） that are known to induce Aphidius ervi flight. Transcriptome sequencing of T22-treated plants infested by aphids showed a remarkable upregulation of genes involved in terpenoids biosynthesis and salicylic acid pathway, which are consistent with the observed flight response ofA. ervi and the VOC bouquet profile underlying this behavioral response.

关键词： defense gene defense priming Macrosiphum euphorbiae multitrophic interactions transcriptome VOCs

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Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis

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World Journal of Gastroenterology 2017年第8期23卷 1458-1468页

作者： Luca Rinaldi Fabio Nascimbeni Mauro Giordano chiara Masetti Barbara Guerrera Annalisa Amelia Maria chiara Fascione Stefano Ballestri Dante Romagnoli rosa Zampino Riccardo Nevola Enrica Baldelli Natalina Iuliano Valerio rosato Amedeo Lonardo Luigi Elio Adinolfi Internal Medicine Clinical Hospital of MarcianiseSecond University of Naples Department of Medical SurgicalNeurologicalMetabolicand Geriatric SciencesSecond University of Naples Outpatient Liver Clinic and Internal Medicine NOCSAEBaggiovaraAzienda USLModena Internal Medicine Pavullo HospitalAzienda Sanitaria Locale

To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related *** prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an age- and Child-Pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were: (1) severity of liver disease at the time of first diagnosis; (2) liver decompensation during follow-up; (3) hepatocellular carcinoma (HCC); (4) orthotopic liver transplantation; and (5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox *** the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-Pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome (12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Child-Pugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-Pugh class ***

关键词： Liver cirrhosis Hepatocellular carcinoma Metabolic syndrome Nonalcoholic fatty liver disease Cardiovascular diseases

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Dose escalation of adalimumab as a strategy to overcome anti-drug antibodies:A case report of infantile-onset inflammatory bowel disease

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World Journal of Gastroenterology 2023年第38期29卷 5428-5434页

作者： Silvana Ancona Sara Signa chiara Longo Giuliana Cangemi Roberta Carfora Enrico Drago Alessandro La rosa Marco Crocco Andrea Chiaro Paolo Gandullia Serena Arrigo Dipartimento di Neuroscienze RiabilitazioneOftalmologiaGenetica e Scienze Materno-Infantili(DINOGMI)Universitàdegli Studi di GenovaGenova 16126Italy Pediatric Gastroenterology and Endoscopy Unit IRCCS Istituto Giannina GasliniGenova 16147Italy Chromatography and Mass Spectrometry Section Central Laboratory of AnalysisIRCCS Istituto Giannina GasliniGenova 16147Italy

BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for *** loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic *** present a case of IO-IBD treated with therapeutic drug monitoring(TDM)-guided high-dose anti-tumor necrosis factor therapy,in which dose escalation monitoring was used as a strategy to overcome anti-drug *** SUMMARY A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life,as well as relapsing perianal abscess and growth ***,anemia,and elevated inflammatory markers were also *** assessment revealed skip lesions with deep colic ulcerations,inflammatory anal sub-stenosis,and deep fissures with persistent abscess.A diagnosis of IO-IBD Crohn-like was *** patient was initially treated with oral steroids and *** the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of *** and biochemical steroid-free remission was achieved with good trough *** 3 mo,antibodies to ADA(ATA)were found with undetectable trough levels;therefore,we optimized the therapy schedule,first administering 10 mg weekly and subsequently up to 20 mg weekly(2.8 mg/kg/dose).After 2 mo of high-dose treatment,ATA disappeared,with concomitant high trough levels and stable clinical and biochemical remission of the *** TDM-guided high-dose ADA treatment as a monotherapy overcame ATA *** strategy could be a good alternative to combination therapy,especially in very young patients.

关键词： Infantile-onset inflammatory bowel disease Adalimumab Loss of response Dose escalation Anti-drug antibodies Case report

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