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Sorafenib delivery nanoplatform based on superpara- magnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

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Nano Research 2017年第7期10卷 2431-2448页

作者： Nicoletta Depalo rosa maria lacobazzi Gianpiero Valente Ilaria Arduino Silvia Villa Fabio Canepa Valentino Laquintana Elisabetta Fanizza Marinella Striccoli Annalisa Cutrignelli Angela Lopedota Letizia Porcelli Amalia Azzariti Massimo Franco maria Lucia Curri Nunzio Denora Istituto per i Processi Chimico-Fisici-CNR UOS Bari Via Orabona 4 70125 Bari Italy Istituto Tumori IRCCS Giovanni Paolo II viale O. Flacco 65 70124 Bari Italy Dipartimento di Chimica Universita degli Studi di Bad Aldo Moro Via Orabona70125 Bari Italy Dipartimento di Farmacia-Scienze del Farmaco Universita degli Studi di Bari Aldo Moro Via Orabona 4 70125 Bari Italy Dipartimento di Chimica e Chimica Industriale Universita di Genova Via Dodecaneso 31 16146 Genova Italy

Currently, sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients. Unfortunately, its side effects, particularly its overall toxicity, limit the therapeutic response that can be achieved. Superparamagnetic iron oxide nanoparticles （SPIONs） are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field, thus improving intratumoral accumulation and reducing adverse effects. Here, nanoformulations based on polyethylene glycol modified phospholipid micelles, loaded with both SPIONs and sorafenib, were successfully prepared and thoroughly investigated by complementary techniques. This nanovector system provided effective drug delivery, had an average hydrodynamic diameter of about 125 nm, had good stability in aqueous medium, and allowed controlled drug loading. Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle. An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver. Human hepatocellular carcinoma （HepG2） cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib. These experiments demonstrated that this delivery platform is able to enhance sorafenib＇s antitumor effectiveness by magnetic targeting. The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites, where selective release of sorafenib can improve its efficacy and safety profile.

关键词： superparamagnetic ironoxide nanoparticles poly(ethylene glycol) (PEG)-modified phospholipidmicelles drug delivery magnetic targeting hepatocellular carcinoma sorafenib

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Integrin-targeting with peptide-bioconjugated semiconductor-magnetic nanocrystalline heterostructures

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Nano Research 2016年第3期9卷 644-662页

作者： Gianpiero Valente Nicoletta Depalo Ivan de Paola rosa maria lacobazzi Nunzio Denora Valentino Laquintana Roberto Comparelli Emiliano Altamura Tiziana Latronico Michele Altomare Elisabetta Fanizza Marinella Striccoli Angela Agostiano Michele Saviano Annarita Del Gatto Laura Zaccaro maria Lucia Curri Universita degli Studi di Bari Aldo Moro Dipartimento di Chimica Via Orabona 4 70125 - Bari Italy Istituto per i Processi Chimico-Fisici-CNR UOS Bari Via Orabona 4 70125 - Bari Italy Istituto di Biostrutture e Bioimmagini-CNR Via Mezzocannone 16 80134 - Napoli Italy Universita degli Studi di Bari Aldo Moro Dipartimento di Farmacia - Scienze del Farmaco Via Orabona 4 70125 - Bari Italy Universita degli Studi di BariAIdo Moro Dipartimento di Bioscienze Biotecnologie e Biofarmaceutica Via Orabona 4 70125 - Bari Italy lstituto di Cristallografia-CNR Via Amendola 122/0 70126 Bari Italy

Binary asymmetric nanocrystals （BNCs）, composed of a photoactive TiO2 nanorod joined with a superparamagnetic γ-Fe203 spherical domain, were embedded in polyethylene glycol modified phospholipid micelle and successfully bioconjugated to a suitably designed peptide containing an RGD motif. BNCs represent a relevant multifunctional nanomaterial, owing to the coexistence of two distinct domains in one particle, characterized by high photoactivity and magnetic properties, that is particularly suited for use as a phototherapy and hyperthermia agent as well as a magnetic probe in biological imaging. We selected the RGD motif in order to target integrin expressed on activated endothelial cells and several types of cancer cells. The prepared RGD-peptide/BNC conjugates, comprehensively monitored by using complementary optical and structural techniques, demon- strated a high stability and uniform dispersibility in biological media. The cytotoxicity of the RGD-peptide/BNC conjugates was studied in vitro. The cellular uptake of RGD-peptide conjugates in the cells, assessed by means of two distinct approaches, namely confocal microscopy analysis and emission spectroscopy determination in cell lysates, displayed selectivity of the RGD-peptide-BNC conjugate for the cw]33 integrin. These RGD-peptide-BNC conjugates have a high potential for theranostic treatment of cancer.

关键词： nanocrystallineheterostructures photoactive semiconductor magnetic nanostructure cyclic RGD peptide αvβ3 integrin active targeting

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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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Analysis of hydrodynamic effects on biofilm thickness in fluidized-bed tapered bioreactors

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Particuology 2021年第5期19卷 48-57页

作者： Daniela maria Koerich Leonardo Machado da rosa Chemical Engineering Department University of Blumenau(FURB)3250 Sao Paulo Street89030-000 BlumenauSanta CatarinaBrazil

Fluidized beds in tapered geometries provide advantages such as a broad range of optimum operating ***,the dynamics of the flow inside these bioreactors is significantly more complex,as they promote non-uniform bioparticles *** this end,the CFD technique can give a detailed description of the flow in the ***,the aim of this work is to assess the influence of the hydrodynamic on the steady-state biofilm thickness through numerical simulations of liquid–solid fluidized *** geometries of tapered bioreactors in the operating conditions used to develop *** were run to solve the two-phase RANS equations using the open-source software OpenFOAM in *** SST k−ω model was used to estimate the turbulent features of the *** and bioparticles distribution inside the reactor were analyzed for different inlet velocities,while bioparticles collision frequency and shear stresses were evaluated for various operating *** comparison between the turbulent kinetic energy and the granular temperature indicated that the fluid flow is more turbulent than the bioparticles *** hydrodynamics influence on the steady-state biofilm thickness was assessed,and results led to the conclusion that biofilm is more sensitive to hydrodynamic shear stress than bioparticles collisions.

关键词： Liquid-solid fluidization Shear stress Particles collisions Computational fluid dynamics Biofilm Tapered bioreactors

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Dehydrated Natural Feed for Cats: Influence on Apparent Digestibility Coefficient, Feces Scores, and Serum Immune, Antioxidant, and Metabolic Biomarkers

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Food and Nutrition Sciences 2024年第7期15卷 594-611页

作者： Bruno Giorgio de Oliveira Cécere Guilherme Luiz Deolindo Bianca F. Bissacotti Priscila Marquezin Copetti maria rosa Chitolina Schetinger Bruna Klein Matheus Delamea Baldissera Thiago Pereira Ribeiro Walter Hugo Cuelho Suarez Daniel Pigatto Monteiro Aleksandro Schafer Da Silva Graduate Multicenter Program in Biochemistry and Molecular Biology University of the State of Santa Catarina Lages Brazil Department of Biochemistry and Molecular Biology Universidade Federal de Santa Maria (UFSM) Santa Maria Brazil Department of Animal Science Universidade Federal de Santa Maria (UFSM) Chapec Brazil Department of Health Science Universidade Franciscana (UFN) Santa Maria Brazil Department of Animal Nutrition Tectron-Tecnologia e Inovao Toledo Brazil

The present study aimed to determine whether natural dehydrated feed (DNF) can replace dry extruded feed while preserving the required daily intake, nutrient digestibility and benefits for immunity and antioxidant response in cats. The animals were divided into two groups of seven animals each. One group received DNF, and the other consumed commercial extruded dry feed (DCF). The experiment lasted 45 days and we measured daily consumption and collected blood and feces samples. The animals in the DNF group showed greater digestibility of fiber and mineral matter than DCF. Cats in the DNF group had a higher volume of feces. DNF cats had lower leukocyte and granulocyte counts and cholesterol levels. Serum enzymatic antioxidant responses and non-enzymatic were higher in DNF cats. Cats in the DNF group showed lower serum acute phase proteins in addition to a tendency toward a higher concentration of transferrin than in the DCF group. Fecal Escherichia coli and total coliform counts of cats fed DNF were higher than DCF. We conclude that the daily consumption of cats is adequate. This feed had greater digestibility of fiber and mineral matter, in addition to an improvement in antioxidant and immunological responses.

关键词： Alternative Feed Antioxidant Companion Animals Health

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In vitro Metabolomic Approaches to Investigating the Potential Biological Effects of Phenolic Compounds:An Update

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Genomics, Proteomics & Bioinformatics 2017年第4期15卷 236-245页

作者： Ursula Catalan Laura Barrubes rosa maria Vails rosa Soila Laura Rubio Functional Nutrition Oxidation and Cardiovascular Diseases Group(NFOC-Salut)Technological Center of Nutrition and Health(CTNS)lnstitut d'lnvestigacio Sanitaria Pere Virgili(IISPV)Faculty of Medicine and ttealth SciencesUniversitat Rovira i VirgiliReus 43201Spain Food Technology Department Universitat de Lleida-AGROTECNIO CenterLleida 25198Spain

Dietary phenolic compounds （PCs） have been receiving intercst lor their presumcd roles ill disease prevention. However, there is a lack of studies on the underlying molecular mechanisnls. In this regard, in vitro metabolomic approaches are suitable for the investigation o1 the molecular changes in response to PC exposure. Up to date, the biological effects of PCs have only been cxalnined for PCs from rosemary （Rosmarinus officinalis）, olive oil, and reSVCl-atrol using cell-based mctabolomic approach, although transcriptomic and/or proteomic studies have also been conducted in the same in vi[ro cell experiment in some cases. Our integral analysis of the reviewed studies suggest that PCs may be involved not only in basic cellular processes or macro-and micro-nutrient meta- bolism, but also in specific metabolic pathways that have been thoroughly investigated. These modulated pathways could have a clinical impact on neurodegenerativc diseases, type 2 diabetes, cancer, and cardiovascular diseases. In conclusion, the in vitro metabolomic approaches provide additional information of the molecular mechanisms involved in disease risk reduction of dietary PCs. In order to elucidate the mechanisms of action of PCs, more metabolomic cell-based studies are nccdcd and testing the physiological conjugated forms of PCs in these cell systems could be of special interest.

关键词： Cell-based Metabolomics Phenolic compounds Mechanism of action Disease prevention

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Cytomegalovirus and inflammatory bowel disease: Is there a link?

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World Journal of Gastroenterology 2006年第30期12卷 4813-4818页

作者： Valeria Criscuoli maria rosa Rizzuto Mario Cottone Division of Internal Medicine Department of General Medicine and Pneumology University of Palermo. " V. Cervello Hospital" Via Trabucco 180 Palermo 90100 Italy Institute of Pathology. " V. Cervello Hospital" Via Trabucco 180 Palermo 90100 Italy

The objective of this report is to give an overall view of the epidemiological, clinical, diagnostic and therapeutic features of Cytomegalovirus （CMV） infection in inflammaton/ bowel disease （IBD）. A review of published reports on this topic was carried out, with particular attention paid to the selection of patients included in studies and the diagnostic methods employed. CMV is frequently associated with IBD. In some cases, CMV infection is as- sociated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. The use of anti-viral therapy in IBD is controversial and an empirical study with controls is needed. The natural history of CMV infection related to the development and treatment of IBD has not been clarified but it is important to take it in consideration because of the possibility of viral persistence in the immunocompromised host and viral interaction with the immune system.

关键词： Cytomegalovirus Inflammatory bowel disease Outcome

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Petiveria alliacea Suppresses Airway Inflammation and Allergen-Specific Th2 Responses in Ovalbumin-Sensitized Murine Model of Asthma

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Chinese Journal of Integrative Medicine 2018年第12期24卷 912-919页

作者： rosa Martha Perez Gutierrez Jose maria Mota Flores Natural Products Research Laboratory Higher School of Chemical Engineering and Extractive IndustriesInstituto Politecnico Nacional (IPN) Professional Unit Adolfo Lopez Mateos Av. Instituto Politécnico NacionalS/N

Objective： To examine the effect of metanol extract of Petiveria alliacea （PM） on airway inflammation in a murine model of chronic asthma. Methods： Two-month-old male BALB/c mice （n=6-8/group） were sensitized on days 0 and 14 by intraperitoneal injection of 20μg ovalbumin （OVA）. On day 25, the mice received an airway challenge with OVA （3%, w/v, in phosphate buffered saline）. PM was administered orally by oral gavage to mice at doses of 100, 200 and 400 mg/kg body weight once daily from days 18 to 23. Control mice were orally administered phosphate buffered saline （PBS） to induce a model of asthma. At the end of the test, respiratory reactivity was assayed, the total cell number, interleukin-4 （IL-4）, IL-5, IL-13, tumor necrosis factor-alpha （TNF-α） and reactive oxygen species （ROS） in the bronchoalveolar lavage fluid （BALF） were determined and the levels of serum IgE, intercellular cell adhesion molecule 1 （ICAM-1） and eotoxin were measured. In addition, lung tissue was used to qualify the IL-4, IL-5, IL-13, TNF-α and transforming growth factor beta 1 （TGF-β1）. Histologic examination was performed to observe inflammatory cellular infiltration. Results： The administration of PM in comparison with the OVA-only treated group significantly attenuated the infiltration of eosinophUs and other inflammatory cells （P〈0.01）. Airway resistance （RI） in the OVA-only induced group was significantly higher than that of the PBS control group （P〈0.01） when methacholine was added. TNF-α, IgE, TGF-β1 and cytokine levels IL-4, IL-5, IL-β in the BALF decreased compared to control mice （P〈0.01 or P〈0.05）. PM treatment also inhibited the production of chemokines, eotaxin and ICAM-1 in BALF （P〈0.01）, which improved lung function. Histopathological examination revealed that the sensitized treated PM groups had significant lower in inflammatory scores similar to dexamethasone treatments and the untreated group. Conclusion： Administration of PM could inhibit airway inflammation, regulate cyt

关键词： Petiveria alliacea allergy antiinflammation asthma

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In Silico and in Vitro Analysis of Pyrazolone Derivatives against Zika Virus and Identification of Potential NS5 Methyltransferase Inhibitors by Molecular Docking

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Journal of Biosciences and Medicines 2024年第7期12卷 214-229页

作者： Luciene Soares Silva Tiago Soares Barbosa maria Leonisa Sanchez-Nuñez Aldenise Mont Serrat rosa da Silva Vitor Won-Held Rabelo Leonardo dos Santos Corrêa Amorim Leonardo Alves Miceli Percilene Fazolin Vegi Alice Bernardino Helena Carla Castro Izabel Christina Nunes de Palmer Paixão Science and Biotechnology Graduate Program Department of Cellular and Molecular Biology Institute of Biology Fluminense Federal University Niteri Brazil Science and Biotechnology Graduate Program Department of Cellular and Molecular Biology Institute of Biology Fluminense Federal University Niterói Brazil Laboratory of Antibiotics Biochemistry Teaching and Molecular Modeling Institute of Biology Fluminense Federal University Niterói Brazil Laboratory of Organic Chemistry at the Institute of Chemistry Institute of Biology Fluminense Federal University Niterói Brazil

Zika virus (ZIKV), a mosquito-borne flavivirus, has been associated with benign infections for decades. However, it has become a public health concern due to its association with severe fetal and neurological complications. Although many efforts have been made to control ZIKV infection, approved vaccines or antiviral drugs are still lacking. Consequently, the development of new effective anti-ZIKV agents is urgently needed. In this context, we investigated the antiviral potential of pyrazolone derivatives against ZIKV replication using in silico and in vitro methods. The four pyrazolone derivatives evaluated (1a, 1b, 1c, and 1d) inhibited over 50% of ZIKV replication with low cytotoxicity. Among them, compound 1b exhibited the most potent activity (EC50 = 4.3 μM) and the highest selectivity (SI = 342). Mechanism of action studies indicated that these compounds act at early stages of virus replication, and compound 1b can also directly inactivate ZIKV particles. Molecular docking studies suggested that these compounds can bind to and block the activity of ZIKV NS5 methyltransferase. Finally, pharmacokinetic and toxicological predictions have reinforced the safety and drug-like profiles of these derivatives. In conclusion, the pyrazolone scaffold proved to be valuable for anti-ZIKV drug development, and the derivatives studied deserve further investigation.

关键词： Zika Pyrazolone NS5 Methyltransferase Antivirals

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Experimental evidence for heritable reproductive time in 2 allochronic populations of pine processionary moth

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Insect Science 2017年第2期24卷 325-335页

作者： Manuela Branco maria-rosa Paiva Helena maria Santos Christian Burban Carole Kerdelhue Centro de Estudos Florestais (CEF) Instituto Superior de Agronomia (ISA) Universidade de Lisboa (ULisboa) 1349-017 Lisboa Portugal CENSE Faculty of Sciences and Technology (FCT) Universidade Nova de Lisboa (UNL) 2829-516 Caparica Portugal INRA Centre de Bordeaux UMR1202 BIOGECO Cestas cedex France INRA Centre de Montpellier UMR CBGP F-34988 Montferrier-sur-Lez cedex France

Phenology allows organisms to overcome seasonally variable conditions through life-cycle adjustment. Changes in phenology can drastically modify the evolutionary tra- jectory of a population, while a shift in the reproductive time may cause allochronic differentiation. The hypothesis of heritable reproductive time was experimentally tested, by studying a unique population of the pine processionary moth Thaumetopoeapityocampa （Den. ＆ Schiff.） which has a shifted phenology, and however co-occurs with the typical population following the classical life cycle. When populations of both types were reared under controlled conditions, the reproductive time was maintained asynchronous, as ob- served in the field. The shifted population was manipulated in the laboratory to reproduce later than usual, yet the offspring emerged in the next year at the expected dates thus ＂com- ing back＂ to the usual cycle. Hybrids from crosses performed between the 2 populations showed an intermediate phenology. From the emergence times of parents and offspring, a high heritability of the reproductive time （h = 0.76） was observed. The offspring ob- tained from each type of cross was genetically characterized using microsatellite markers. Bayesian clustering analysis confirmed that hybrids can he successfully identified and separated from the parental genetic classes by genotyping. Findings support the hypothesis that, for this particular population, incipient allochronic speciation is due to a heritable shift in the reproductive time that further causes assortative mating and might eventually cause ecological adaptation/maladaptation in response to environmental changes.

关键词： allochronic speciation experimental crossings heritability phenology reproductive isolation Thaumetopoeapityocampa

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