Aptamer-conjugated, fluorescent gold nanorods as potential cancer theradiagnostic agents

Funding for this project was provided by the ERC grant StG242991.GNRs are emerging as a new class of probes for theradiagnostic applications thanks to their unique optical properties. However, the achievement of proper nanoconstructs requires the synthesis of highly pure GNRs with well-defined aspect ratio (AR), in addition to extensive surface chemistry modification to provide them with active targeting and, possibly, multifunctionality. In this work, we refined the method of the seed mediated growth and developed a robust procedure for the fabrication of GNRs with specific AR. We also revealed and characterized unexplored aging phenomena that follow the synthesis and consistently alter GNRs' final AR. Such advances appreciably improved the feasibility of GNRs fabrication and offered useful insights on the growth mechanism. We next produced fluorescent, biocompatible, aptamer-conjugated GNRs by performing ligand exchange followed by bioconjugation to anti-cancer oligonucleotide AS1411. In vitro studies showed that our nanoconstructs selectively target cancer cells while showing negligible cytotoxicity. As a result, our aptamer-conjugated GNRs constitute ideal cancer-selective multifunctional probes and promising candidates as photothermal therapy agents.Publisher PDFPeer reviewe

1H–NMR fingerprinting and supervised pattern recognition to evaluate the stability of virgin olive oil during storage

Metabolomic fingerprinting of virgin olive oil (VOO) by 1H NMR spectroscopy was used to study its stability during storage simulating normal shelf life conditions during its commercialization. A representative set of VOOs covering the full range of possible chemical compositions were exposed to light (500 lux for 12 h/day) at 25 °C for 12 months or stored in the dark at 25 °C, 30 °C and 35 °C for 24 months. Multivariate data analysis of the 1H NMR spectra of the oil samples provided classification models to evaluate VOO freshness and to verify the light exposure of the VOO during storage, as well as regression models to determine VOO storage time and tentatively the best before date of a fresh VOO. These predictive models disclosed the chemical compounds responsible for the compositional changes in VOO due to hydrolytic and oxidative degradation taking place during its storage, and confirmed that light and increasing temperature enhance these processes. The presence of characteristic resonances of hydroperoxides (primary oxidation products) and the decrease of 1H signals assigned to phenolic compounds, mainly secoiridoid derivatives, and other minor compounds such as fatty acids, squalene and native (E)-2-hexenal present in fresh VOO revealed its oxidative degradation. Further, the emergence of low intensity 1H signals of saturated aldehydes meant that the secondary oxidation process has started at a low rate and yield. Moreover, the decrease of the 1H signals of triacylglycerides and sn-1,2-diacylglycerides, and the increase of sn-1,3-diacylglycerides indicated that hydrolytic degradation of VOO and diacylglyceride isomerisation was occurring. 1H NMR fingerprint of VOO together with pattern recognition techniques afford relevant information to assess the quality of VOOs taking into consideration legal, sensory and health-promoting aspects.Fil: Alonso Salces, Rosa Maria. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Gallo, Blanca. Universidad del País Vasco; EspañaFil: Collado, María Isabel. Universidad del País Vasco; EspañaFil: Sasía Arriba, Andrea. Universidad del País Vasco; EspañaFil: Viacava, Gabriela Elena. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Grupo de Investigación en Ingeniería en Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: García González, Diego Luis. Universidad Pablo de Olavide; EspañaFil: Gallina Toschi, Tullia. Universidad de Bologna; ItaliaFil: Servili, Maurizio. Università di Perugia; ItaliaFil: Berrueta, Luis Ángel. Universidad del País Vasco; Españ

Gold nanorod reshaping in vitro and in vivo using a continuous wave laser

Funding for this project was provided by ERC grant 242991 (D. Elson), and by Cancer Research UK via the CRUK Cancer Imaging Centre at the Institute of Cancer Research (ICR) to J. Bamber. We acknowledge an ERC starting grant (project number 257182) to A. Porter, and BRC funding (project number P46143) to A. Porter, D. Elson and P. Ruenraroengsak. We acknowledge NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden (J. Bamber) and at Imperial College London, as well as support provided by the Cancer Research UK Imperial Centre.Gold nanorods (GNRs) are increasingly being investigated for cancer theranostics as they possess features which lend themselves in equal measures as contrast agents and catalysts for photothermal therapy. Their optical absorption spectral peak wavelength is determined by their size and shape. Photothermal therapy using GNRs is typically established using near infrared light as this allows sufficient penetration into the tumour matrix. Continuous wave (CW) lasers are the most commonly applied source of near infrared irradiation on GNRs for tumour photothermal therapy. It is perceived that large tumours may require fractionated or prolonged irradiation. However the true efficacy of repeated or protracted CW irradiation on tumour sites using the original sample of GNRs remains unclear. In this study spectroscopy and transmission electron microscopy are used to demonstrate that GNRs reshape both in vitro and in vivo after CW irradiation, which reduces their absorption efficiency. These changes were sustained throughout and beyond the initial period of irradiation, resulting from a spectral blue-shift and a considerable diminution in the absorption peak of GNRs. Solid subcutaneous tumours in immunodeficient BALB/c mice were subjected to GNRs and analysed with electron microscopy pre- and post-CW laser irradiation. This phenomenon of thermally induced GNR reshaping can occur at relatively low bulk temperatures, well below the bulk melting point of gold. Photoacoustic monitoring of GNR reshaping is also evaluated as a potential clinical aid to determine GNR absorption and reshaping during photothermal therapy. Aggregation of particles was coincidentally observed following CW irradiation, which would further diminish the subsequent optical absorption capacity of irradiated GNRs. It is thus established that sequential or prolonged applications of CW laser will not confer any additional photothermal effect on tumours due to significant attenuations in the peak optical absorption properties of GNRs following primary laser irradiation.Publisher PDFPeer reviewe

Valutazione della stabilità dell'ollio d'oliva vergine in conservazione mediante profilo 1H-NMR e chemiometria

La qualità dell'ollio vergine di oliva (VOO) è correlata alla sue proprietà sensoriali e nutrizionali, alla stabilità ossidativa e alla sua conservazione. L'ossidazione del VOO porta alla formazione di sostanze sgradevoli, alla degradazione dei suoi antiossidanti bioattivi e all'accumulo di composti di degradazione, causando la persita delle sua qualità sensoriali e salutari, del suo valore economico e dell'accettazione da parte dei consumatori. La resistenza del VOO all'ossidazione dipende dalla sua composizione chimica e dalla sua esposizione a fattori pro-ossidante come ossigeno, luce e temperatura. La stabilità del VOO durante la conservazione è stata studiata mediante un approccio metabolomico non mirato basato sull'impronta digitale 1H-NMR e sul riconoscimento del modello che simula le normali condizioni di conservazione durante la sua commercializzazione.Fil: Alonso Salces, Rosa Maria. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Gallo, Blanca. Universidad del País Vasco; EspañaFil: Poliero, Aimará Ayelen. Universidad Nacional de Mar del Plata; ArgentinaFil: Viacava, Gabriela Elena. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Grupo de Investigación en Ingeniería en Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: García González, Diego Luis. Instituto de la Grasa; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Gallina Toschi, Tullia. Universidad de Bologna; ItaliaFil: Servili, Maurizio. Università di Perugia; ItaliaFil: Berrueta, Luis Angel. Universidad del País Vasco; Españ

Agricultural by-products with bioactive effects: A multivariate approach to evaluate microbial and physicochemical changes in a fresh pork sausage enriched with phenolic compounds from olive vegetation water

The use of phenolic compounds derived from agricultural by-products could be considered as an eco-friendly strategy for food preservation. In this study a purified phenol extract from olive vegetation water (PEOVW) was explored as a potential bioactive ingredient for meat products using Italian fresh sausage as food model. The research was developed in two steps: first, an in vitro delineation of the extract antimicrobial activities was performed, then, the PEOVW was tested in the food model to investigate the possible application in food manufacturing. The in vitro tests showed that PEOVW clearly inhibits the growth of food-borne pathogens such as Listeria monocytogenes and Staphylococcus aureus. The major part of Gram-positive strains was inhibited at the low concentrations (0.375–3 mg/mL). In the production of raw sausages, two concentrates of PEOVW (L1:0.075% and L2: 0.15%) were used taking into account both organoleptic traits and the bactericidal effects. A multivariate statistical approach allowed the definition of the microbial and physicochemical changes of sausages during the shelf life (14 days). In general, the inclusion of the L2 concentration reduced the growth of several microbial targets, especially Staphylococcus spp. and LABs (2 log10 CFU/g reduction),while the increasing the growth of yeasts was observed. The reduction of microbial growth could be involved in the reduced lipolysis of raw sausages supplemented with PEOVWas highlighted by the lower amount of diacylglycerols. Moisture and aw had a significant effect on the variability of microbiological features,while food matrix (the sausages' environment) can mask the effects of PEOVW on other targets (e.g. Pseudomonas). Moreover, the molecular identification of the main representative taxa collected during the experimentation allowed the evaluation of the effects of phenols on the selection of bacteria. Genetic data suggested a possible strain selection based on storage time and the addition of phenol compounds especially on LABs and Staphylococcus spp. The modulation effects on lipolysis and the reduction of several microbial targets in a naturally contaminated product indicates that PEOVW may be useful as an ingredient in fresh sausages for improving food safety and quality

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/ 27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality