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Is there a relationship between dopamine and rhegmatogenous retinal detachment?

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Neural Regeneration Research 2020年第2期15卷 311-314页

作者： Alessio Martucci Massimo Cesareo Maria Dolores Pinazo-Durán michela Di Pierro Matteo Di Marino Carlo Nucci Massimiliano Coletta Raffaele Mancino Ophthalmology Unit Department of Experimental MedicineUniversity of Rome Tor VergataRomeItaly Ophthalmic Research Unit "Santiago Grisolia"/FISABIO and Cellular-Molecular Ophthalmobiology Group/University of Valencia ValenciaSpain Department of Clinical Sciences and Translational Medicine University of Rome Tor VergataRomeItaly

Dopamine and its receptors have been widely studied in the neurological conditions and in the retina. In this study, we evaluated the possible role of dopamine in rhegmatogenous retinal detachment(RRD) by comparing the amount of 3,4-dihydroxyphenylacetic acid(DOPAC), a surrogate index of retinal dopamin levels, in the vitreous sample of patients affected by RRD with those affected by macular pucker and vitre ous hemorrhage. Our results showed that significantly higher levels of DOPAC were found in the vitreou sample of patients affected by RRD compared with those affected by vitreous hemorrhage and macula pucker(P = 0.002). Specifically, no trace of the substance was found in vitreous hemorrhage and macula pucker samples. A slightly significant positive correlation was found among DOPAC and post-operativ best corrected visual acuity(r = 0.470, P = 0.049). No correlation was found between DOPAC and the day elapsed between diagnosis and surgery(P = 0.317). For the first time our findings suggest that DOPAC i released in RRD, but not in other retinal diseases such as vitreous hemorrhage and macular pucker. More over, we showed a correlation between visual acuity outcome and the amount of DOPAC in the vitreous This might have a potential, although still unknown, implication in the pathogenesis of the disease and/o in the associated photoreceptors loss. This study was approved by the Ethics Committee of Rome Tor Ver gata University Hospital(R.S.92.10) on September 24, 2010.

关键词： 3,4-dihydroxyphenylacetic acid DOPAC dopamine dopaminergic amacrine cells dopaminergic neurotoxicity macular pucker oxidative stress photoreceptor degeneration rhegmatogenous retinal detachment vitreous hemorrhage

Seismic Retrofitting Techniques for Existing Masonry Buildings

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Journal of Civil Engineering and Architecture 2011年第11期5卷 1011-1018页

作者： Antonio Gesualdo michela Monaco Department of Structural Engineering University of Naples "Federico II" Department of "Cultura del Progetto" S. U. N. Second University of Naples

In many seismically active regions of the world there are large numbers of masonry buildings. Most of these buildings have not been designed for seismic loads. Recent earthquakes have shown that many of these buildings are seismically vulnerable and should be considered for retrofitting. Different conventional and unconventional retrofitting techniques are available to increase the strength and/or ductility of unreinforced masonry （URM） walls. This paper reviews and discusses seismic retrofitting of masonry walls with emphasis on the conventional techniques. Retrofitting procedures are discussed with regard to a case study： a stone masonry building in lrpinia region, damaged by the 1980 earthquake. The interventions are evaluated by means of finite elements with a macroelement obtained with a homogenization technique. Linear and nonlinear procedures are compared, and peculiarities of each procedure are shown.

关键词： Masonry homogenization seismic behaviour retrofitting techniques.

The Ins and Outs of the Rice AGAMOUS Subfamily

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Molecular Plant 2013年第3期6卷 650-664页

作者： Ludovico Dreni michela Osnato Martin M. Kater Department of Biosciences Università degli Studi di Milano via Celoria 26 20133 Milan Italy

Genes of the AGAMOUS subfamily have been shown to play crucial roles in reproductive organ identity determination, fruit, and seed development. They have been deeply studied in eudicot species and especially in Arabidopsis. Recently, the AGAMOUS subfamily of rice has been studied for their role in flower development and an enormous amount of data has been generated. In this review, we provide an overview of these data and discuss the conservation of gene functions between rice and Arabidopsis.

关键词： transcriptional control and transcription factors floral development reproductive biology Arabidopsis rice.

Multivalent interacting glycodendrimer to prevent amyloid-peptide fibril formation induced by Cu（II）： A multidisciplinary approach

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Nano Research 2018年第3期11卷 1204-1226页

作者： Anna Janaszewska Barbara Klajnert-Maculewicz Monika MarcinkowskaI Piotr Duchnowicz Dietmar Appelhans Gianvito Grasso Marco A. Deriu Andrea Danani michela Cangiotti Maria Francesca Ottaviani Department of General Biophysics Faculty of Biology and Environmental Protection University of Lodz 90-236 Lodz Poland Department of Biophysics of Environmental Pollution Faculty of Biology and Environ mental Protection University of Lodz 90-236 Lodz Poland Department Bioactive and Responsive Polymers Leibniz Institute of Polymer Research 01069 Dresden Germany SUPSI-DTI IDSIA- Dalle Molle Institute forArtificial Intelligence CH-6928 Manno Switzerland Department of Pure and Applied Sciences University of Urbino 61029 Urbino Italy

Amyloid peptide fibrillogenesis induced by Cu（II） ions is a key event in the pathogenesis of Alzheimer＇s disease. Dendrimers have been found to be active in preventing fibril formation. Therefore, they hold promise for the treatment of Alzheimer＇s disease. In this study, the fibrillation mechanism of amyloid peptide Aβ 1-40 was studied by adding Cu（II） in the absence and presence of 4th generation poly（propyleneimine） glycodendrimer functionalized with sulfate groups, using dynamic light scattering （DLS）, circular dichroism （CD）, fluorescence, electron paramagnetic resonance （EPR） and molecular modeling （MD）. The glycodendrimer was non-toxic to mHippoE-18 embryonic mouse hippocampal cells, selected as a nerve cell model and decreased the toxicity of peptide aggregates formed after the addition of Cu（II）. The binary systems of Cu（II）-glycodendrimer, Cu（II）-peptide, and glycodendrimer-peptide were first characterized. At the lowest Cu（II）/glycodendrimer molar ratios, Cu（II） was complexed by the internal-dendrimer nitrogen sites. After saturation of these sites, Cu（II） binding with sulfate groups occurred. Stable Cu（II）-peptide complexes formed within 5 min and were responsible for a transition from an α helix to a β-sheet conformation of Aβ 1-40. Glycodendrimer-peptide interactions provoked the stabilization of the a-helix, as demonstrated in the absence of Cu（II） by the Thioflavin T assay, and in the presence of Cu（II） by CD, EPR, and MD. Formation of fibrils is differentially modulated by glycodendrimer and Cu（II） concentrations for a fixed amount of Aβ 1-40. Therefore, this multidisciplinary study facilitated the recognition of optimal experimental conditions that allow the glycodendrimer to avoid the fibril formation induced by Cu（II）.

关键词： glycodendrimers amyloid peptide Cu(II) circular dichroism (CD) electron paramagneticresonance (EPR) molecular modeling

Mucosal adhesion and anti-inflammatory effects of Lactobacillus rhamnosus GG in the human colonic mucosa: A proof-of-concept study

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World Journal of Gastroenterology 2018年第41期24卷 4652-4662页

作者： Cristiano Pagnini Vito Domenico Corleto michela Martorelli Claudio Lanini Giancarlo D'Ambra Emilio Di Giulio Gianfranco Delle Fave Department of Digestive and Liver Disease School of Medicine and PsychologyS.Andrea HospitalSapienza University

AIM To investigate the adhesion and anti-inflammatory effects of Lactobacil us rhamnosus GG (LGG) in the colonic mucosa of healthy and ulcerative colitis (UC) patients, both in vivo and ex vivo in an organ culture *** For the ex vivo experiment, a total of 98 patients (68 UC patients and 30 normal subjects) were included. Endoscopic biopsies were collected and incubated with and without LGG or LGG-conditioned media to evaluate the mucosal adhesion and anti-inflammatory effects [reduction of tumor necrosis factor alpha (TNFα) and interleukin (IL)-17 expression] of the bacteria, and extraction of DNA and RNA for quantification by real-time (RT)-PCR occurred after the incubation. A dose-response study was performed by incubating biopsies at "regular", double and 5 times higher doses of LGG. For the in vivo experiment, a total of 42 patients (20 UC patients and 22 normal controls) were included. Biopsies were taken from the colons of normal subjects who consumed a commercial formulation of LGG for 7 d prior to the colonoscopy,and the adhesion of the bacteria to the colonic mucosa was evaluated by RT-PCR and compared with that of control biopsies from patients who did not consume the formulation. LGG adhesion and TNFα and IL-17 expression were compared between UC patients who consumed a regular or double dose of LGG supplementation prior to *** In the ex vivo experiment, LGG showed consistent adhesion to the distal and proximal colon in normal subjects and UC patients, with a trend towards higher concentrations in the distal colon, and in UC patients, adhesion was similar in biopsies with active and quiescent inflammation. In addition, bioptic samples from UC patients incubated with LGG conditioned media (CM) showed reduced expression of TNFα and IL-17 compared with the corresponding expression in controls (P < 0.05). Incubation with a double dose of LGG increased mucosal adhesion and the anti-inflammatory effects (P < 0.05). In the in vivo expe

关键词： Lactobacillus rhamnosus GG Ulcerative colitis Probiotic Adhesion Cytokines

Neuroretinal dysfunction in patients affected by neurofibromatosis type 1

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International Journal of Ophthalmology(English edition) 2022年第5期15卷 773-779页

作者： Antonietta Moramarco Luca Lucchino Fabiana Mallone michela Marcelli Ludovico Alisi Vincenzo Roberti Sandra Giustini Alessandro Lambiase Marcella Nebbioso Department of Sense Organs Sapienza University of RomePoliclinico Umberto IRome 00161Italy Department of Dermatology and Venereology Sapienza University of RomePoliclinico Umberto IRome 00161Italy

AIM:To examine neuroretinal function by using the multifocal electroretinography(mf ERG)test in patients with neurofibromatosis type 1(NF1)without optic pathway gliomas(OPGs).METHODS:This study was conducted on 35 patients(35 eyes)with NF1 and 30 healthy subjects(30 eyes)for the control *** subject underwent a complete ophthalmological examination including spectral domainoptical coherence tomography(SD-OCT)and mf *** 1.5-Tesla magnetic resonance imaging(MRI)scan of the brain was performed in NF1 patients to assess the presence of *** participants were recruited having a best corrected visual acuity(BCVA)of no less than 20/20 in each *** amplitude and implicit time of the P1 wave(first-order Kernel component)were evaluated on mf *** analysis was carried out in the two central degrees and in the four quadrants from two to 25 degrees of visual ***:Statistically significant results were obtained for the P1 wave amplitudes in the 4 quadrants in NF1 patients compared to healthy controls,while the reduction was not significant in the 2 central degrees between the groups.A statistically significant difference was observed among the P1 wave amplitudes as recorded in the 4 quadrants within the NF1 group,with lower amplitudes detected in the nasal *** differences in the implicit times were recorded in the 2 central degrees and in the 4 quadrants as compared between NF1 patients and ***:Impaired neuroretinal function in NF1 patients is expressed in a decreased amplitude of the P1-wave between 2 and 25 central retinal degrees on mf *** intracellular signal transduction due to abnormal neurofibromin-mediated cyclic adenosine monophosphate(c AMP)generation,can be *** possible use of mf ERG as subclinical retinal damage indicator has a potential utility in clinical practice for the follow-up of NF1 patients.

关键词： neurofibromatosis type 1 multifocal electroretinography neuroretinal function optic pathway gliomas neurofibromin

Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第29期25卷 3870-3896页

作者： Elena De Mattia Erika Cecchin michela Guardascione Luisa Foltran Tania Di Raimo Francesco Angelini Mario D’Andrea Giuseppe Toffoli Clinical and Experimental Pharmacology Centro di Riferimento Oncologico di Aviano (CRO) IRCCS Aviano (PN) 33081 Italy Department of Medical Oncology Centro di Riferimento Oncologico di Aviano (CRO) IRCCS Aviano (PN) 33081 Italy Medical Oncology and Anatomic Pathology Unit “San Filippo Neri Hospital” Rome 00135 Italy Department of Oncology “San Filippo Neri Hospital” Rome 00135 Italy

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., resection, liver transplantation, percutaneous ablation). Treatments with palliative intent include chemoembolization and systemic therapy. Among systemic treatments, the small-molecule multikinase inhibitor sorafenib has been the only systemic treatment available for advanced HCC over 10 years. More recently, other smallmolecule multikinase inhibitors (e.g., regorafenib, lenvatinib, cabozantinib) have been approved for HCC treatment. The promising immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) are still under investigation in Europe while in the US nivolumab has already been approved by FDA in sorafenib refractory or resistant patients. Other molecules, such as the selective CDK4/6inhibitors (e.g., palbociclib, ribociclib), are in earlier stages of clinical development, and the c- MET inhibitor tivantinib did not show positive results in a phase III study. However, even if the introduction of targeted agents has led to great advances in patient response and survival with an acceptable toxicity profile, a remarkable inter-individual heterogeneity in therapy outcome persists and constitutes a significant problem in disease management. Thus, the identification of biomarkers that predict which patients will benefit from a specific intervention could significantly affect decision-making and therapy planning. Germ-line variants have been suggested to play an important role in determining outcomes of HCC systemic therapy in terms of both toxicity and treatment efficacy. Particularly, a number of studies have focused on the role of genetic polymorphisms impacting the drug metabolic pathway and membrane translocation as well as the drug mechanism of action as predictive/prognostic markers of HCC treatment. The aim of this review is to summarize and

关键词： Hepatocellular carcinoma Pharmacogenetics Genetic markers Sorafenib Regorafenib Immune checkpoint inhibitors Cytochromes UDP glucuronosyltransferase 1A

The promise of liquid biopsy in cancer:a clinical perspective

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Chinese Journal of Cancer Research 2015年第5期27卷 488-490页

作者： Enrico Cortesi michela Palleschi Valentina Magri Giuseppe Naso Medical Oncology Unit Department of Radiological Oncological and Pathological SciencesSapienzaUniversity of Rome

The clinical utility of liquid biopsy in cancer treatment will increase as circulating tumor cells （CTCs） analysis move from the enumeration to the real-time measurement of tumor characteristics. Intratumor heterogeneity is becoming increasingly recognized as a major drawback to the shift to personalized medicine. Spatial and temporal heterogeneity might be reflected by the serial assessment of CTCs. Indeed, the developing technologies for CTCs analysis now allow digital genomic and next- generation sequencing approaches, able to differentiate molecular subtypes of the disease and to monitor genetic variation over time. The liquid biopsy of cancer might offer a real-time assessment of tumor biology, providing the opportunity to serially evaluate patients most likely to benefit from targeted drugs based on a dynamic characterization of the disease at the molecular level. Mthough hurdles remain before liquid biopsy is seen in routine clinical practice, the information derived from CTCs may facilitate the real-time identification of actionable mutations in cancer leading the way toward personalized medicine.

关键词： Circulating tumor cells (CTCs) breast liquid biopsy cancer

Hepatocellular carcinoma:Surgical perspectives beyond the barcelona clinic liver cancer recommendations

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World Journal of Gastroenterology 2014年第24期20卷 7525-7533页

作者： Alfredo Guglielmi rea Ruzzenente Simone Conci Alessro Valdegamberi Marco Vitali Francesca Bertuzzo michela De Angelis Guido Mantovani Calogero Iacono Department of Surgery Division of General Surgery AUnit of Hepato-Pancreatico-Biliary surgeryUniversity of Verona Medical School37134 VeronaItaly

The barcelona clinic liver cancer(BCLC)staging system has been approved as guidance for hepatocellular carcinoma(HCC)treatment guidelines by the main Western clinical liver *** to the BCLC classification,only patients with a small single HCC nodule without signs of portal hypertension or hyperbilirubinemia should undergo liver *** contrast,patients with intermediate-advanced HCC should be scheduled for palliative therapies,even if the lesion is *** studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by liver ***,this classification has been criticised because it excludes many patients who could benefit from curative *** aim of this review was to evaluate the role of surgery beyond the BCLC *** liver resection can be performed in patients with portal hypertension and well-compensated liver function with a 5-year survival rate of 50%.Surgery also offers good long-term result in selected patients with multiple or large HCCs with a reported 5-year survival rate of over 50%and 40%,*** macrovascular invasion is associated with a poor prognosis,liver resection provides better long-term results than palliative therapies or best supportive ***,researchers have identified several genes whose altered expression influences the prognosis of patients with *** genes may be useful for classifying the biological behaviour of different tumours.A revision of the BCLC classification should be introduced to provide the best treatment strategy and to ensure the best prognosis in patients with HCC.

关键词： Hepatocellular carcinoma Liver resection Hepatectomy Barcelona clinic liver cancer Surgical therapy