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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 model.METHODS 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 colonoscopy.RESULTS 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 experiment, LGG was detectable only in the colon of

关键词： Lactobacillus rhamnosus GG Ulcerative colitis Probiotic Adhesion Cytokines

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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 critically discuss the pharmacogenetic literatu

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

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Inclusive Playgrounds:A Reality or a Utopia in Our Cities?

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Journal of Civil Engineering and Architecture 2020年第12期14卷 635-643页

作者： michela Dalpra Department of Civil Environmental and Mechanical Engineering(DICAM)University of TrentoTrento 38123Italy

The culture of inclusion needs to be continuously promoted,supported,strengthened and tested to remove the barriers and deficiencies still present in the built environment around us.Do the play areas in parks,gardens and squares offer real opportunities for persons with different abilities to play and have fun?Do they promote the principle of integration and create opportunities for inclusion?To answer these questions,an audit tool has been developed to assess the inclusivity of outdoor play areas in the central and suburban areas of our cities.The key elements of the evaluation focus on the physical environment of the playground and are grouped in three thematic areas:physical and sense-perception accessibility;accessibility to the experience and participation and socialisation.Although children’s right to play is now recognised and there is much talk of inclusion,application of the tool to an Italian city has shown that the right to play is not fully and satisfactorily applied.Inclusive playgrounds are still not frequent enough and a new approach to their design is needed.

关键词： Playground inclusion accessibility children with disabilities

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Technologies Applied to Cultural Heritage： A Robot Application in Architectural Survey

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Journal of Civil Engineering and Architecture 2012年第9期6卷 1109-1116页

作者： michela Cigola Department of Civil & Mechanical Engineering University of Cassino Cassino 03043 Italy

In this work a study of feasibility is illustrated to design and build a mobile robot for inspection and analysis of historical sites of architectonic interest. This novel application for robotic systems can be considered of great interest because nowadays the need of more and more accurate and efficient survey activity requires enhancement and even development of procedures with more reliable, innovative, and advanced characteristics. Within this expectation robots and robotic systems seem to be suitable solutions even with the purposes of: operating in environments that cannot be reached by human operators. The study of feasibility concerns with the analysis and simulation of a robotic system that can be used for operating in historical sites. Basic features of such mobile robots, either legged or wheeled, are well known, but specific requirements should be considered for the proposed applications in archaeological/architectural sites, which can be considered as a novelty in the field of Robotics. Basic features of the proposed robotic system can be summarized as follows: the robot should be able to move inside the archaeological and/or architectural sites by carrying surveying devices and by avoiding damage of the surface and other parts of the site.

关键词：机器人应用建筑学文化遗产轮式移动机器人机器人系统技术历史遗迹调查活动

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Can cyclin-dependent kinase 4/6 inhibitors convert inoperable breast cancer relapse to operability? A case report

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World Journal of Clinical Cases 2020年第3期8卷 517-521页

作者： michela Palleschi Roberta Maltoni Eleonora Barzotti Elisabetta Melegari Annalisa Curcio Lorenzo Cecconetto Samanta Sarti Silvia Manunta Andrea Rocca Department of Medical Oncology Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori(IRST)IRCCSMeldola 47014Italy Breast Surgery Unit Ospedale Morgagni-PierantoniForlì47121Italy

BACKGROUND Pathological complete response(pCR) is rare in hormone receptor-positive(HR+)HER2-negative breast cancer(BC) treated with either endocrine therapy(ET) or chemotherapy. Radical resection of locoregional relapse, although potentially curative in some cases, is challenging when the tumor invades critical structures.The oral cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ET has obtained a significant increase in objective response rates and progression-free survival in patients with advanced BC and is now being evaluated in the neoadjuvant setting. We present a clinical case of a patient with an inoperable locoregional relapse of HR+ HER2-negative BC who experienced p CR after treatment with palbociclib.CASE SUMMARY We report the clinical case of a 60-year-old patient who presented with an inoperable locoregional relapse of HR+, HER2-negative BC 10 years after the diagnosis of the primary tumor. During a routine follow-up visit, breast magnetic resonance imaging and positron emission tomography/computed tomography revealed a 4-cm lesion in the right subclavicular region, infiltrating the chest wall and extending to the subclavian vessels, but without bone or visceral involvement. Treatment was begun with palbociclib plus letrozole, converting the disease to operability over a period of 6 mo. Surgery was performed and a p CR achieved. Of note, during treatment the patient experienced a very uncommon toxicity characterized by burning tongue and glossodynia associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. A reduction in the dose of palbociclib did not provide relief and treatment with the inhibitor was thus discontinued, resolving the tongue symptoms. Laboratory exams were unremarkable. Given that this was a late relapse, the tumor was classified asendocrine-sensitive, a condition associated with high sensitivity to palbociclib.CONCLUSION This case highlights the potential of the cyclin-dependent kinase 4/6 inhibitor plus ET combination to achieve pCR in locoregional

关键词： Hormone receptor-positive advanced breast cancer Endocrine therapy Cyclin-dependent kinase 4/6 inhibitor Pathological complete response

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role of microRNAs in the main molecular pathways of hepatocellular carcinoma

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World Journal of Gastroenterology 2018年第25期24卷 2647-2660页

作者： Francesco Vasuri michela Visani Giorgia Acquaviva Thomas Brand michelangelo Fiorentino Annalisa Pession Giovanni Tallini Antonia D’Errico Dario de Biase Department of Experimental Diagnostic and Specialty Medicine(DIMES)S.Orsola-Malpighi HospitalUniversity of BolognaBologna 40138Italy Department of Medicine(Dipartimento di Medicina Specialistica Diagnostica e Sperimentale)Molecular Diagnostic UnitAzienda USL di BolognaUniversity of Bologna-School of MedicineBologna 40138Italy Department of Pharmacy and Biotechnology(Dipartimento di Farmacia e Biotecnologie) University of BolognaBologna 40127Italy Department of Pharmacy and Biotechnology(Dipartimento di Farmacia e Biotecnologie) Molecular Diagnostic UnitAzienda USL di BolognaUniversity of BolognaBologna 40138Italy

Hepatocellular carcinoma(HCC) is the most common primary liver malignant neoplasia. HCC is characterized by a poor prognosis. The need to find new molecular markers for its diagnosis and prognosis has led to a progressive increase in the number of scientific studies on this topic. MicroRNAs(miRNAs) are small noncoding RNA that play a role in almost all main cellular pathways. miRNAs are involved in the regulation of expression of the major tumor-related genes in carcinogenesis, acting as oncogenes or tumor suppressor genes. The aim of this review was to identify papers published in 2017 investigating the role of miRNAs in HCC tumorigenesis. miRNAs were classified according to their role in the main molecular pathways involved in HCC tumorigenesis:(1) m TOR;(2) Wnt;(3) JAK/STAT;(4) apoptosis; and(5) MAPK. The role of miRNAs in prognosis/response prediction was taken into consideration. Bearing in mind that the analysis of miRNAs in serum and other body fluids would be crucial for clinical management, the role of circulating miRNAs in HCC patients was also investigated. The most represented mi RNA-regulated pathway in HCC is m TOR, but apoptosis, Wnt, JAK/STAT or MAPK pathways are also influenced by mi RNA expression levels. These miRNAs could thus be used in clinical practice as diagnostic, prognostic or therapeutic targets for HCC treatment.

关键词： MicroRNA Molecular pathway mTOR Prognosis Hepatocellular carcinoma Review

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Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis

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World Journal of Gastroenterology 2011年第36期17卷 4099-4103页

作者： michela Barollo Valentina Medici Renata DIncà Antara Banerjee Giuseppe Ingravallo Marco Scarpa Surajit Patak Cesare Ruffolo Romilda Cardin Giacomo Carlo Sturniolo Department of Surgical and Gastroenterological Sciences University of PadovaPadova 35128Italy Department of Internal Medicine Division of Gastroenterology and HepatologyUniversity of CaliforniaDavisCA 95616United States Department of Pathology University of BariBari 70121Italy Department of Oncological Surgery Veneto Oncological InstitutePadova 35128Italy

AIM:To evaluate whether combination therapy with antitumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis.METHODS:Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d.The experimental mice were then randomised into the following subgroups:standard diet + DSS treated (induced colitis group);standard diet + DSS + subcutaneous 25 μg anti-TNFα treated group;Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα;standard diet + DSS + subcutaneous 6.25 μg anti-TNFα treated group and Zn acetate treated group + DSS + subcutaneous 6.25 μg anti-TNFα.Each group of mice was matched with a similar group of sham control animals.Macroscopic and histological features were scored blindly.Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (8OH-dG) as a measure of oxidative damage.RESULTS:DSS produced submucosal erosions,ulcers,inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or combined with zinc.The effect was more pronounced in the latter group (vs Zn diet,P < 0.02).Myeloperoxidase activity (vs controls,P < 0.02) and DNA adducts,greatly elevated in the DSS fed colitis group (vs controls,P < 0.05),were significantly reduced in the treated groups,with a more remarkable effect in the group receiving combined therapy (vs standard diet,P < 0.04).CONCLUSION:DSS induces colonic inflammation which is modulated by the administration of anti-TNFα.Combining anti-TNFα with Zn acetate offers marginal benefit in colitis severity.

关键词：肿瘤坏死因子综合治疗醋酸锌结肠炎抗氧化实验性 DNA加合物过氧化物酶活性

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Chromosome Scale Genome Assembly andTranscriptome Profiling of Nannochloropsisgaditana in Nitrogen Depletion

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Molecular Plant 2014年第2期7卷 323-335页

作者： Elisa Corteggiani Carpinelli Andrea Telatin Nicola Vitulo Claudio Forcato michela D’Angelo Riccardo Schiavon Alessandro Vezzi Giorgio Mario Giacometti Tomas Morosinotto Giorgio Valle CRIBI Biotechnology Centre University of Padua Padua 35121 Italy Department of Biology University of Padua Padua 35121 Italy

Nannochloropsis is rapidly emerging as a model organism for the study of biofuel production in microalgae.Here, we report a high-quality genomic assembly of Nannochloropsis gaditana, consisting of large contigs, up to 500 kbplong, and scaffolds that in most cases span the entire length of the chromosomes. We identified 10646 complete genesand characterized possible alternative transcripts. The annotation of the predicted genes and the analysis of cellular pro-cesses revealed traits relevant for the genetic improvement of this organism such as genes involved in DNA recombina-tion, RNA silencing, and cell wall synthesis. We also analyzed the modification of the transcriptional profile in nitrogendeficiencyma condition known to stimulate lipid accumulation. While the content of lipids increased, we did not detectmajor changes in expression of the genes involved in their biosynthesis. At the same time, we observed a very signifi-cant down-regulation of mitochondrial gene expression, suggesting that part of the AcetyI-CoA and NAD（P）H, normallyoxidized through the mitochondrial respiration, would be made available for fatty acids synthesis, increasing the fluxthrough the lipid biosynthetic pathway. Finally, we released an information resource of the genomic data of IV. gaditana,available online at ***.

关键词： Nannochloropsis lipids biofuel genome transcriptome de novo assembly SOLiD nitrogen deprivation chromosomes telomeres

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Transcranial direct current stimulation enhances theory of mind in Parkinson’s disease patients with mild cognitive impairment:a randomized,double-blind,sham-controlled study

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Translational Neurodegeneration 2019年第1期8卷 1-13页

作者： Mauro Adenzato Rosa Manenti Ivan Enrici Elena Gobbi michela Brambilla Antonella Alberici Maria Sofia Cotelli Alessandro Padovani Barbara Borroni Maria Cotelli Department of Psychology University of TurinTurinItaly Neuroscience Institute of Turin TurinItaly Neuropsychology Unit IRCCS Istituto Centro San Giovanni di Dio–FatebenefratelliBresciaItaly Department of Philosophy and Educational Sciences University of Turinvia Gaudenzio Ferrari 910124 TurinItaly Centre for Neurodegenerative Disorders Neurology UnitDepartment of Clinical and Experimental SciencesUniversity of BresciaBresciaItaly

Background:Parkinson’s Disease(PD)with mild cognitive impairment(MCI)(PD-MCI)represents one of the most dreaded complications for patients with PD and is associated with a higher risk of developing dementia.Although transcranial direct current stimulation(tDCS)has been demonstrated to improve motor and non-motor symptoms in PD,to date,no study has investigated the effects of tDCS on Theory of Mind(ToM),i.e.,the ability to understand and predict other people’s behaviours,in PD-MCI.Methods:In this randomized,double-blind,sham-controlled study,we applied active tDCS over the medial frontal cortex(MFC)to modulate ToM performance in twenty patients with PD-MCI.Twenty matched healthy controls(HC)were also enrolled and were asked to perform the ToM task without receiving tDCS.Results:In the patients with PD-MCI,i)ToM performance was worse than that in the HC,ii)ToM abilities were poorer in those with fronto-executive difficulties,and iii)tDCS over the MFC led to significant shortening of latency for ToM tasks.Conclusions:We show for the first time that active tDCS over the MFC enhances ToM in patients with PD-MCI,and suggest that non-invasive brain stimulation could be used to ameliorate ToM deficits observed in these patients.

关键词： Medial frontal cortex(MFC) Mild cognitive impairment(MCI) Parkinson’s disease(PD) Theory of mind(ToM) Transcranial direct current stimulation(tDCS)

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Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease

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World Journal of Gastroenterology 2009年第20期15卷 2506-2511页

作者： Valter Donadon Massimiliano Balbi michela Ghersetti Silvia Grazioli Antonio Perciaccante Giovanni Della Valentina Rita Gardenal Maria Dal Mas Pietro Casarin Giorgio Zanette Cesare Miranda Department of Medicine Internal Medicine 3rd Pordenone Hospital Diabetes Clinic Pordenone Hospital Via Montereale 24 Pordenone 33170 Italy

AIM:To explore the association between hepatocellular carcinoma(HCC) and type 2 diabetes mellitus, describe the temporal relations between the onset of diabetes and the development of HCC and evaluate the possible effects of antidiabetic therapy on HCC risk.METHODS:We recruited 465 HCC patients, 618 with cirrhosis and 490 control subjects.We evaluated the odds ratio(OR) for HCC by univariate and multivariate analysis.Moreover, OR for HCC in diabetic subjects treated with insulin or sulphanylureas and with metformin were calculated.RESULTS:The prevalence of diabetes mellitus was 31.2% in HCC, 23.3% in cirrhotic patients and 12.7% in the Control group.By univariate and multivariate analysis, the OR for HCC in diabetic patients were respectively 3.12(CI 2.2-4.4, P < 0.001) and 2.2(CI 1.2-4.4, P = 0.01).In 84.9% of cases, type 2 diabetes mellitus was present before the diagnosis of HCC.Moreover, we report an OR for HCC of 2.99(CI 1.34-6.65, P = 0.007) in diabetic patients treated with insulin or sulphanylureas, and an OR of 0.33(CI 0.1-0.7, P = 0.006) in diabetic patients treated with metformin.CONCLUSION:Our study confi rms that type 2 diabetes mellitus is an independent risk factor for HCC and pre-exists in the majority of HCC patients.Moreover, in male patients with type 2 diabetes mellitus, our data shows a direct association of HCC with insulin and sulphanylureas treatment and an inverse relationship with metformin therapy.

关键词：肝癌治疗风险降糖 2型糖尿病肝病慢性二甲双胍

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