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Micro RNAs as lung cancer biomarkers

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World Journal of Clinical Oncology 2014年第4期5卷 604-620页

作者： Valerio Del Vescovo Margherita Grasso Mattia Barbareschi michela A Denti Laboratory of RNA Biology and Biotechnology Centre for Integrative Biology University of Trento Unit of Surgical Pathology Laboratory of Molecular Pathology Trentino Biobank S.Chiara Hospital

Lung cancer is the leading cause of cancer mortality worldwide. Its high mortality is due to the poor prognosis of the disease caused by a late disease presentation, tumor heterogeneities within histological subtypes, and the relatively limited understanding of tumor biology. Importantly, lung cancer histological subgroups respond differently to some chemotherapeutic substances and side effects of some therapies appear to vary between subgroups. Biomarkers able to stratify for the subtype of lung cancer, prognosticate the course of disease, or predict the response to treatment are in high demand. In the last decade, microR NAs(miR NAs), measured in resected tumor samples or in fine needle aspirate samples have emerged as biomarkers for tumor diagnosis, prognosis and prediction of response to treatment, due to the ease of their detection and in their extreme specificity. Moreover, miR NAs present in sputum, in plasma, in serum or in whole blood have increasingly been explored in the last five years as less invasive biomarkers for the early detection of cancers. In this review we cover the increasing amounts of datathat have accumulated in the last ten years on the use of miR NAs as lung cancer biomarkers.

关键词： Lung cancer Non-small cell lung carcinomas MicroRNAs Biomarkers

Hyperplasia vs hypertrophy in tissue regeneration after extensive liver resection

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World Journal of Gastroenterology 2017年第10期23卷 1764-1770页

作者： Fabio Marongiu michela Marongiu Antonella Contini Monica Serra Erika Cadoni Riccardo Murgia Ezio Laconi Experimental Medicine Unit Department of Biomedical SciencesUniversity of Cagliari09124 CagliariItaly

To address to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue *** ability of the liver to regenerate is remarkable on both clinical and biological grounds. Basic mechanisms underlying this process have been intensively investigated. However, it is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system. We were able to follow the fate of single transplanted hepatocytes during the regenerative response elicited by 2/3 partial surgical hepatectomy (PH) in rats. Clusters of transplanted cells were 3D reconstructed and their size distribution was evaluated over time after *** size and liver DNA content were largely recovered 10 d post-PH, as expected (e.g., total DNA/liver/100 g b.w. was 6.37 ± 0.21 before PH and returned to 6.10 ± 0.36 10 d after PH). Data indicated that about 2/3 of the original residual hepatocytes entered S-phase in response to PH. Analysis of cluster size distribution at 24, 48, 96 h and 10 d after PH revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes increased at 24 h (248.50 μm2 ± 7.82 μm2, P = 0.0015), but returned to control values throughout the regenerative process (up to 10 d post-PH, 197.9 μm2 ± 6.44 μm2, P = 0.11). A sizeable fraction of the remnant hepatocyte population does not participate actively in tissue mass *** stands as the major mechanism contributing to liver mass restoration after PH, with hypertrophy playing a transient role in the process.

关键词： Liver regeneration Hypertrophy Hyperplasia

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： Architectural survey robotics technologies for cultural heritage.

Dual stimuli-responsive polyurethane-based hydrogels as smart drug delivery carriers for the advanced treatment of chronic skin wounds

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Bioactive Materials 2021年第9期6卷 3013-3024页

作者： Rossella Laurano Monica Boffito michela Abrami Mario Grassi Alice Zoso Valeria Chiono Gianluca Ciardelli Politecnico di Torino Mechanical and Aerospace Engineering DepartmentCorso Duca degli Abruzzi 2410129TorinoItaly Universitàdegli Studi di Trieste Department of Engineering and ArchitectureVia Alfonso Valerio 6/134127TriesteItaly

The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close *** this work,a thermo-and pH-responsive hydrogel(P-CHP407)was prepared from an ad hoc synthesized amphiphilic poly(ether urethane)(CHP407)exposing a significant amount of-COOH groups(8.8±0.9 nmol/g_(polymer)).The exposure of acid moieties in P-CHP407 hydrogel led to slightly lower initial gelation temperature(12.1◦C vs.14.6◦C,respectively)and gelation rate than CHP407 hydrogel,as rheologically *** hydrogel characterization by Low Field NMR(LF-NMR)spectroscopy suggested that the presence of carboxylic groups in P-CHP407 caused the formation of bigger micelles with a thicker hydrated shell than CHP407 hydrogels,as further proved by Dynamic Light Scattering *** addition,P-CHP407 hydrogel showed improved capability to change its internal pH compared to CHP407 one when incubated with an alkaline buffer(pH 8)(e.g.,pH_(change_5min)=3.76 and 1.32,respectively).Moreover,LF-NMR characterization suggested a stronger alkaline-pH-induced interaction of water molecules with micelles exposing-COOH ***,the hydrogels were found biocompatible according to ISO 10993 and able to load and release Ibuprofen:delivery kinetics of Ibuprofen was enhanced by P-CHP407 hydrogels at alkaline pH,suggesting their potential use as smart delivery systems in the treatment of chronic infected wounds.

关键词： Stimuli-responsive hydrogel Drug delivery system pH-triggered release Advanced wound treatment Polyurethane hydrogel LF-NMR characterization

Between Algorithm and Model:Different Molecular Surface Definitions for the Poisson-Boltzmann Based Electrostatic Characterization of Biomolecules in Solution

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Communications in Computational Physics 2013年第1期13卷 61-89页

作者： Sergio Decherchi Jose Colmenares Chiara Eva Catalano michela Spagnuolo Emil Alexov Walter Rocchia Department of Drug Discovery and Development Istituto Italiano di Tecnologiavia Morego3016163 GenovaItaly Institute for Applied Mathematics and Information Technologies National Research Council of ItalyGenoaItaly Department of Physics Clemson UniversityClemsonSouth CarolinaUSA

The definition of a molecular surface which is physically sound and computationally efficient is a very interesting and long standing problem in the implicit solvent continuum modeling of biomolecular systems as well as in the molecular graphics *** this work,two molecular surfaces are evaluated with respect to their suitability for electrostatic computation as alternatives to the widely used Connolly-Richards surface:the blobby surface,an implicit Gaussian atom centered surface,and the skin *** figures of merit,we considered surface differentiability and surface area continuity with respect to atom positions,and the agreement with explicit solvent *** analysis seems to privilege the skin to the blobby surface,and points to an unexpected relationship between the non connectedness of the surface,caused by interstices in the solute volume,and the surface area dependence on atomic *** order to assess the ability to reproduce explicit solvent results,specific software tools have been developed to enable the use of the skin surface in PoissonBoltzmann calculations with the DelPhi *** results indicate that the skin and Connolly surfaces have a comparable performance from this last point of view.

关键词： Molecular surface Connolly surface blobby surface skin surface Poisson-Boltzmann

Liver pathology in COVID-19 related death and leading role of autopsy in the pandemic

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World Journal of Gastroenterology 2023年第1期29卷 200-220页

作者： Martina Zanon Margherita Neri Stefano Pizzolitto Davide Radaelli Monica Concato michela Peruch Stefano D'Errico Department of Medical Surgical and Health Sciences University of TriesteTrieste 34149Italy Department of Medical Sciences University of FerraraFerrara 44121Italy Department of Pathology Santa Maria della Misericordia University HospitalUdine 33100Italy

BACKGROUND Information on liver involvement in patients with coronavirus disease 2019 is currently *** To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome coronavirus 2 positive *** A systematic literature search on PubMed was carried out until June 21,*** A literature review reveals that pre-existing liver disease and elevation of liver enzyme in these patients are not common;liver enzyme elevations tend to be seen in those in critical *** the poor expression of viral receptors in the liver,it seems that the virus is able to infect this organ and therefore cause liver ***,to date,the search for the virus inside the liver is not frequent(16%of the cases)and only a small number show the presence of the *** most of the autopsy cases,macroscopic assessment is lacking,while microscopic evaluation of livers has revealed the frequent presence of congestion(42.7%)and steatosis(41.6%).Less frequent is the finding of hepatic inflammation or necrosis(19%)and portal inflammation(18%).The presence of microthrombi,frequently found in the lungs,is infrequent in the liver,with only 12%of cases presenting thrombotic formations within the vascular *** To date,the greatest problem in interpreting these modifications remains the association of the damage with the direct action of the virus,rather than with the inflammation or alterations induced by hypoxia and hypovolemia in patients undergoing oxygen therapy and decompensated patients.

关键词： Liver COVID-19 Autopsy Immunohistochemistry In situ hybridization Immunofluorescence

Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells

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World Journal of Gastroenterology 2020年第33期26卷 4900-4918页

作者： michela Anna Polidoro Joanna Mikulak Valentina Cazzetta Ana Lleo Domenico Mavilio Guido Torzilli Matteo Donadon Hepatobiliary Immunopathology Laboratory Humanitas Clinical and Research Center–IRCCSRozzano 20089MilanItaly Laboratory of Clinical and Experimental Immunology Humanitas Clinical and Research Center-IRCCSRozzano 20089MilanItaly Department of Medical Biotechnologies and Translational Medicine(BioMeTra) University of MilanRozzano 20089MilanItaly Department of Biomedical Science Humanitas UniversityPieve Emanuele 20090MilanItaly Department of Internal Medicine Humanitas Clinical and Research Center–IRCCSRozzano 20089MilanItaly Department of Hepatobiliary and General Surgery Humanitas Clinical and Research Center-IRCCSRozzano 20089MilanItaly

In the last years,several studies have been focused on elucidate the role of tumor microenvironment(TME)in cancer development and *** TME,cells from adaptive and innate immune system are one of the main abundant *** dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor *** important cross-talk has been elucidate for several kind of tumors and occurs also in patients with liver cancer,such as hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA).Liver is well-known to be an important immunological organ with unique ***,in normal conditions,the rich immune-infiltrating cells cooperate with non-parenchymal cells,such as liver sinusoidal endothelial cells and Kupffer cells,favoring self-tolerance against gut *** presence of underling liver immunosuppressive microenvironment highlights the importance to dissect the interaction between HCC and iCCA cells with immune infiltrating cells,in order to understand how this cross-talk promotes tumor *** attention is,in fact,focused on immune-based therapy for these tumors,as promising approach to counteract the intrinsic anti-tumor activity of this *** this review,we will examine the key pathways underlying TME cell-cell communications,with deeper focus on the role of natural killer cells in primary liver tumors,such as HCC and iCCA,as new opportunities for immune-based therapeutic strategies.

关键词： Primary liver cancer Natural killer cells Tumor microenvironment Hepatocellular carcinoma Intrahepatic cholangiocarcinoma Immune cells

Early endoscopic ultrasonography in acute biliary pancreatitis: A prospective pilot study

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World Journal of Gastroenterology 2015年第36期21卷 10427-10434页

作者： Andrea Anderloni Marianna Galeazzi Marco Ballarè michela Pagliarulo Marco Orsello Mario Del Piano Alessandro Repic Digestive Endoscopy Unit Division of GastroenterologyHumanitas Research Hospital Gastrointestinal and Endoscopy Unit AOU "Maggiore della Carità"28100 NovaraItaly

AIM: To investigate the clinical usefulness of early endoscopic ultrasonography(EUS) in the management of acute biliary pancreatitis(ABP).METHODS: All consecutive patients entering the emergency department between January 2010 and December 2012 due to acute abdominal pain and showing biochemical and/or radiological findings consistent with possible ABP were prospectively enrolled. Patients were classified as having a low,moderate,or high probability of common bile duct(CBD) stones,according to the established risk stratification. Exclusion criteria were: gastrectomy or patient in whom the cause of biliary obstruction was already identified by ultrasonography. All enrolled patients underwent EUS within 48 h of their admission. Endoscopic retrograde cholangiopancreatography was performed immediately after EUS only in those cases with proven CBD stones or sludge. The following parameters were investigated:(1) clinical: age,sex,fever;(2) radiological: dilated CBD; and(3) biochemical: bilirubin,AST,ALT,g GT,ALP,amylase,lipasis,PCR. Association between presence of CBD stone at EUS and the individual predictors wereassessed by univariate logistic regression. Predictors significantly associated with CBD stones(P 38 females,53.5%,mean age 58 ± 20.12 years,range 27-89 years; 33 males,46.5%,mean age 65 ± 11.86 years,range 41-91 years) were included in the present study. The probability of CBD stones was considered low in 21 cases(29%),moderate in 26(37%),and high in the remaining 24(34%). The 71 patients included in the study underwent EUS,which allowed for a complete evaluation of the target sites in all the cases. The procedure was completed in a mean time of 14.7 min(range 9-34 min),without any notable *** overall CBD

关键词： Acute biliary pancreatitis Choledocolithiasis Comm

Microbiota and the gut-liver axis:Bacterial translocation,inflammation and infection in cirrhosis

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World Journal of Gastroenterology 2014年第45期20卷 16795-16810页

作者： Valerio Giannelli Vincenza Di Gregorio Valerio Iebba michela Giusto Serena Schippa Manuela Merli Ulrich Thalheimer Gastroenterology Department of Clinical Medicine Sapienza University of Rome Department of Public Health and Infectious Diseases Sapienza University of Rome The Exeter Liver Unit Royal Devon and Exeter Foundation Trust

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.

关键词： Dysbiosis Cirrhosis Bacterial translocation Inflammation Infection Bacterial overgrowth Rifaximine Lactulose Liver Gut Portal hypertension