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Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： antonio masone Chiara Zucchelli Enrico Caruso Giovanna musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NmR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life sciences University of InsubriaVareseItaly

PrPsc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

serological surveillance for sARs-CoV-2 antibodies among students,faculty and staff within a large university system during the pandemic

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World Journal of Virology 2025年第1期14卷 99-107页

作者： marcos G Pinheiro Gabriela G O Alves maria Eduarda R Conde sofia L Costa Regina C s sant’Anna Isa m F Antunes mônica C Carneiro Fabio s Ronzei Julia C scaffo Felipe R Pinheiro Lialyz s Andre Helvecio C Povoa Valéria T Baltar Fabíola Giordani Eduarda s Hemerly Gisele C Alexandre Karla C de Paula márcio Watanabe antonio Claudio L da Nóbrega Jackeline Christiane P Lobato Fabio Aguiar-Alves Laboratory of molecular Epidemiology and Biotechnology Rodolpho Albino University LaboratoryFluminense Federal UniversityNiterói 24241000Rio de JaneiroBrazil Estácio de sáUniversity Nova Friburgo 28611135Rio de JaneiroBrazil Pathology Program Medicine schoolFluminense Federal UniversityNiterói 24070090Rio de JaneiroBrazil Department of Pharmaceutical sciences Lloyd L.Gregory School of PharmacyPalm Beach Atlantic UniversityWest Palm BeachFL 33401United States Health Institute of Nova Friburgo Fluminense Federal UniversityNova Friburgo 28613001Rio de JaneiroBrazil Department of Epidemiology and Biostatistics Institute of Collective Health(ISC)Fluminense Federal UniversityNiterói 24033900Rio de JaneiroBrazil Institute of Physical Education Fluminense Federal UniversityNiterói 24020005Rio de JaneiroBrazil Department of statistics Fluminense Federal UniversityNiterói 24210200Rio de JaneiroBrazil Department of Physiology and Pharmacology Fluminense Federal UniversityNiterói 24210130Rio de JaneiroBrazil

BACKGROUND At the end of December 2019,the world faced severe acute respiratory syndrome-coronavirus 2(sARs-CoV-2),which led to the outbreak of coronavirus disease 2019(COVID-19),associated with respiratory *** virus has shown significant challenges,especially for senior citizens,patients with other underlying illnesses,or those with a sedentary *** tests conducted early on have helped identify how the virus is transmitted and how to curb its *** study hypothesis was that the rapid serological test for sARs-CoV-2 antibodies could indicate the immunoreactive profile during the COVID-19 pandemic in a university *** To conduct active surveillance for serological expression of anti-sARs-CoV-2 antibodies in individuals within a university setting during the COVID-19 *** This sectional study by convenience sampling was conducted in a large university in Niteroi-RJ,Brazil,from march 2021 to July *** study population consisted of students,faculty,and administrative staff employed by the university.A total of 3433 faculty members,60703 students,and 3812 administrative staff were invited to *** were gathered through rapid serological tests to detect immunoglobulin(Ig)m and IgG against ***χ²or Fisher's exact test was used to conduct statistical analysis.A 0.20 significance level was adopted for variable selection in a multiple logistic regression model to evaluate *** A total of 1648 individuals were enrolled in the *** proportion of COVID-19 positivity was 164/1648(9.8%).The adjusted logistic model indicate a positive association between the expression of Igm or IgG and age[odds ratio(OR)=1.16,95%CI:1.02-1.31](Ps who had been in contact with a COVID-19-positive case(OR=3.49,95%CI:2.34-5.37)(Pse who had received the COVID-19 vaccine(OR=2.33,95%CI:1.61-3.35)(Psocial isolation(OR=0.59,95%CI:0.41-0.84)(Psho

关键词： serological surveillance sARs-CoV-2 antibodies COVID-19 serological rapid test Risk factors for COVID-19

Oleogels for development of health-promoting food products

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Food science and Human Wellness 2020年第1期9卷 31-39页

作者： Artur J.martins antonio A.Vicente lorenzo m.Pastrana miguel A.Cerqueira International Iberian Nanotechnology Laboratory Av.Mestre JoséVeiga s/n4715-330BragaPortugal Centre of Biological Engineering University of MinhoCampus de Gualtar4710-057BragaPortugal

metabolic health and the maintenance of good levels of triglycerides,high-density lipoprotein cholesterol,blood pressure and glucose levels are concerns that can greatly impact human quality of *** consumers’demands,together with technological innovations,have led to a diversification of the food *** fostering of off-the-shelf available and affordable healthy food products is necessary,as detrimental effects on human health from the ingestion of saturated fat sources urge the efforts to find *** can be tailored using specific triglycerides and oleogelators,that can be selected to yield targeted fatty acids,reduce higher levels of cholesterol with competing binding-molecules(***),reduce saturated fat content,lessen appetite(*** the shape of foods)or carry exclusive bioactive compounds to be absorbed in the digestive *** are foreseen as an important technological advance in food science due to their versatility,easy processing and *** review explored the strategies in place to develop and produce oleogels,foreseeing their introduction in foods and how they might represent an important source of functionality through the use of healthy *** also explored how oleogels can act on the human overall metabolic health if they are used in human diet.

关键词： Oleogel Vagal pathway Nutrition Fatty acids metabolism Gut-brain axis

Endoscopic techniques for the diagnosis of pancreatic cystic lesions

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World Journal of Gastroenterology 2025年第1期31卷 1-7页

作者： sahib singh saurabh Chandan Rakesh Vinayek Jahnvi Dhar Jayanta samanta Gabriele Capurso Ivo Boskoski Cristiano spada Jorge D machicado stefano Francesco Crinò antonio Facciorusso Department of Internal medicine Sinai HospitalBaltimoreMD 21215United States Division of Gastroenterology and Hepatology Creighton University School of MedicineOmahaNE 68131United States Department of Gastroenterology Sinai Hospital of BaltimoreBaltimoreMD 21215United States Department of Gastroenterology Postgraduate Institute of Medical Education and ResearchChandigarh 160012India Division of Pancreato-Biliary Endoscopy and Endosonography Pancreas Translational and Clinical Research CenterIRCCS San Raffaele Scientific InstituteVita-Salute San Raffaele UniversityMilano 20132Italy Digestive Endoscopy Unit Fondazione Policlinico Universitario Agostino Gemelli IRCSSUniversitàCattolica del Sacro Cuore di RomaCenter for Endoscopic Research Therapeutics and TrainingRoma 00168Italy Department of Gastroenterology and Endoscopy Catholic UniversityRoma 00168Italy Department of Gastroenterology University of Michigan HealthAnn ArborMI 48107United States Department of Endoscopy University of VeronaVerona 37121VenetoItaly Gastroenterology Unit Department of Medical and Surgical SciencesUniversity of FoggiaFoggia 71122Italy

Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other *** accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUs)and various techniques based on that such as EUs-guided fine needle aspiration,EUs-guided needle confocal laser endomicroscopy,EUs-through-the-needle biopsy,and contrast-enhanced *** studies have reported varying diagnostic and adverse event rates with these *** addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different *** this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.

关键词： Endoscopic ultrasound Fine needle aspiration Needle confocal laser endomicroscopy Through-the-needle biopsy Contrast-enhanced endoscopic ultrasound

Effect of Noisy Fitness in Real-Time strategy Games Player Behaviour Optimisation Using Evolutionary Algorithms

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Journal of Computer science & Technology 2012年第5期27卷 1007-1023页

作者： antonio m. mora antonio Fernndez-Ares Juan J. merelo Pablo García-snchez Carlos m. Fernandes Computer Architecture and Technology Department University of Granada Institute for systems and Robotics Technical University of Lisbon

This paper investigates the performance and the results of an evolutionary algorithm （EA） specifically designed for evolving the decision engine of a program （which, in this context, is called bot） that plays Planet Wars. This game, which was chosen for the Google Artificial Intelligence Challenge in 2010, requires the bot to deal with multiple target planets, while achieving a certain degree of adaptability in order to defeat different opponents in different scenarios. The decision engine of the bot is initially based on a set of rules that have been defined after an empirical study, and a genetic algorithm （GA） is used for tuning the set of constants, weights and probabilities that those rules include, and therefore, the general behaviour of the bot. Then, the bot is supplied with the evolved decision engine and the results obtained when competing with other bots （a bot offered by Google as a sparring partner, and a scripted bot with a pre-established behaviour） are thoroughly analysed. The evaluation of the candidate solutions is based on the result of non-deterministic battles （and environmental interactions） against other bots, whose outcome depends on random draws as well as on the opponents＇ actions. Therefore, the proposed GA is dealing with a noisy fitness function. After analysing the effects of the noisy fitness, we conclude that tackling randomness via repeated combats and reevaluations reduces this effect and makes the GA a highly valuable approach for solving this problem.

关键词： real-time strategy game genetic algorithm noisy fitness player behaviour optimisation parameter adaptation

Combined locoregional treatment of patients withhepatocellular carcinoma： state of the art

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World Journal of Gastroenterology 2016年第6期22卷 1935-1942页

作者： Roberto Iezzi maurizio Pompili Alessandro Posa Giuseppe Coppola antonio Gasbarrini lorenzo Bonomo Department of Bioimaging Institute of Radiology“A.Gemelli”Hospital-Catholic University00168 RomeItaly Department of Internal medicine “A.Gemelli”Hospital-Catholic University00168 RomeItaly

In recent years, a combination of intervention therapies has been widely applied in the treatment of hepatocellular carcinoma(HCC). One such combined strategy is based on the combination of the percutaneous approach, such as radiofrequency ablation(RFA), and the intra-arterial locoregional approach, such as trans-arterial chemoembolization(TACE). several types of evidence have supported the feasibility and benefit of combined therapy, despite some studies reporting conflicting results and outcomes. The aim of this review was to explain the technical aspects of different combined treatments and to comprehensively analyze and compare the clinical efficacy and safety of this combined treatment option and monotherapy, either as TACE or RFA alone, in order to provide clinicians with an unbiased opinion and valuable information. Based on a literature review and our experience, combined treatment seems to be a safe and effective option in the treatment of patients with early/intermediate HCC when surgical resection is not feasible; furthermore, this approach provides better results than RFA and TACE alone for the treatment of large HCC, defined as those exceeding 3 cm in size. It can also expand the indication for RFA to previously contraindicated "complex cases", with increased risk of thermal ablation related complications due to tumor location, or to "complex patients" with high bleeding risk.

关键词： Hepatocellular carcinoma Combinedtreatment chemoembolization ablation microwave

Autoimmune pancreatitis not otherwise specified(NOs): Clinical features and outcomes of the forgotten type

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Hepatobiliary & Pancreatic Diseases International 2019年第6期18卷 576-579页

作者： Nicolò de Pretis Filippo Vieceli Alessandro Brandolese lorenzo Brozzi antonio Amodio Luca Frulloni Gastroenterology Unit Pancreas Center University of Verona

Background:Autoimmune pancreatitis(AIP)is a well-recognized fibroinflammatory disease of the *** the significant number of studies published on AIP type 1 and 2,no studies have been focused on AIP type not otherwise specified(NOs)and therefore very little is known about clinical features and long-term outcomes of these *** aim of this study was to investigate clinical and radiological features of AIP type ***:Patients classified as AIP type NOs at clinical onset included in our database prospectively maintained since 1995 were ***,clinical data were collected and ***:Forty-six patients were included in the *** clinical onset was mainly characterized by weight loss,jaundice and acute *** patients(17.4%)were reclassified as AIP type 2 during follow-up because of the development of ulcerative *** patients(15.2%)experienced relapse after steroid treatment but only one(2.2%)needed immunosuppressive drugs because of recurrent ***:AIP type NOs shares clinical features similar to AIP type 2 and a relevant proportion of patients was reclassified as AIP type 2 during follow-up because of the development of ulcerative *** risk of relapse is low but not irrelevant.

关键词： Autoimmune pancreatitis Not otherwise specified Outcome Follow-up Therapy

Nanostructural Evolution of sugarcane Rind and Pith submitted to Hydrothermal Pretreatments

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Journal of Renewable materials 2018年第2期6卷 152-159页

作者： marcelo m.Oliveira antonio A.s.Curvelo Carlos Driemeier Brazilian Bioethanol science and Technology Laboratory(CTBE) Brazilian Center for Research in Energy and Materials(CNPEM)Caixa Postal 619213083-970CampinasSão PauloBrasil são Carlos school of Engineering(EEsC) University of São Paulo(USP)Caixa Postal 78013560-970São CarlosSão PauloBrasil são Carlos Institute of Chemistry(IQsC) University of São Paulo(USP)Caixa Postal 78013560-970São CarlosSão PauloBrasil

Lignocellulose conversion into cellulosic ethanol and coproducts starts with a pretreatment *** current industrial plants of cellulosic ethanol use thermochemical pretreatments under hydrothermal conditions,with or without addition of acid *** pretreatments modify biomass chemistry and morphology,particularly at the *** this work,we use X-ray diffraction,dynamic vapor sorption and calorimetric thermoporometry to investigate the biomass nanostructural changes promoted by hydrothermal *** compare and differentiate the rind and pith fractions of sugarcane stalks in order to contribute to the understanding of rind-pith contrasting ***,for both cane fractions our results point consistently to cellulose co-crystallization,lignin aggregation,and opening of nanoscale pores as the main nanostructural phenomena occurring during hydrothermal treatments.

关键词： Cellulose bagasse sugarcane cellulosic ethanol pretreatment

Infrastructure for collaborative science and societal applications in the Columbia River estuary

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Frontiers of Earth science 2015年第4期9卷 659-682页

作者： antonio m. BAPTIsTA NsF science and Technology Center for Coastal margin Observation & Prediction Oregon Health & science University Portland Oregon 97239 USA Oregon Health & science University Astoria Oregon 97103 USA Portland state University Portland Oregon 97201 USA Applied Physics Laboratory of the University of Washington Seattle Washington 98105 USA Oregon state University Corvallis Oregon 97331 USA Formerly University of maryland Center for Environmental studies Maryland 21613 USA

To meet societal needs, modem estuarine science needs to be interdisciplinary and collaborative, combine discovery with hypotheses testing, and be responsive to issues facing both regional and global stakeholders. such an approach is best conducted with the benefit of data-rich environments, where information from sensors and models is openly accessible within convenient timeframes. Here, we introduce the operational infrastruc- ture of one such data-rich environment, a collaboratory created to support （a） interdisciplinary research in the Columbia River estuary by the multi-institutional team of investigators of the science and Technology Center for Coastal margin Observation ＆ Prediction and （b） the integration of scientific knowledge into regional decision making. Core components of the operational infrastructure are an observation network, a modeling system and a cyber-infrastructure, each of which is described. The observation network is anchored on an extensive array of long-term stations, many of them interdisciplinary, and is complemented by on-demand deployment of temporary stations and mobile platforms, often in coordinated field campaigns. The modeling system is based on finite- element unstructured-grid codes and includes operational and process-oriented simulations of circulation, sediments and ecosystem processes. The flow of information is managed through a dedicated cyber-infrastructure, con- versant with regional and national observing systems.

关键词： estuaries observations numerical modeling,cyber-infrastructure Columbia River