349 research outputs found
Book of Abstracts of the 8th International Symposium on Delivery of Functionality in Complex Food Systems
This volume contains the abstracts presented at the 8th International Symposium on Delivery of Functionality in Complex Food Systems, held in Sheraton Porto Hotel Conference Centre, Porto, Portugal, 7-10 July, 2019.info:eu-repo/semantics/publishedVersio
β-lactoglobulin micro- and nanostructures as bioactive compounds vehicle: In vitro studies
β-Lactoglobulin (β-Lg) is known to be capable to bind hydrophilic and hydrophobic bioactive compounds. This research aimed to assess the in vitro performance of β-Lg micro- (diameter ranging from 200 to 300 nm) and nano (diameter < 100 nm) structures associated to hydrophilic and hydrophobic model compounds on Caco-2 cells and under simulated gastrointestinal (GI) conditions. Riboflavin and quercetin were studied as hydrophilic and hydrophobic model compounds, respectively. Cytotoxicity experiment was conducted using in vitro cellular model based on human colon carcinoma Caco-2 cells. Moreover, the digestion process was simulated using the harmonized INFOGEST in vitro digestion model, where samples were taken at each phase of digestion process - oral, gastric and intestinal - and characterized in terms of particle size, polydispersity index (PDI), surface charge by dynamic light scattering (DLS); protein hydrolysis degree by 2,4,6-trinitrobenzene sulfonic acid (TNBSA) assay and native polyacrylamide gel electrophoresis; and bioactive compound concentration. Caco-2 cell viability was not affected up to 21 Ă 10â3 mg mLâ1 of riboflavin and 16 Ă 10â3 mg mLâ1 quercetin on β-Lg micro- and nanostructures. In the oral phase, β-Lg structuresâ particle size, PDI and surface charge values were not changed comparing to the initial β-Lg structures (i.e., before being subjected to in vitro GI digestion). During gastric digestion, β-Lg structures were resistant to proteolytic enzymes and to acid environment of the stomach â confirmed by TNBSA and native gel electrophoresis. In vitro digestion results indicated that β-Lg micro- and nanostructures protected both hydrophilic and hydrophobic compounds from gastric conditions and deliver them to target site (i.e., intestinal phase). In addition, β-Lg structures were capable to enhance riboflavin and quercetin bioaccessibility and bioavailability potential compared to bioactive compounds in their free form. This study indicated that β-Lg micro- and nanostructures were capable to enhance hydrophilic and hydrophobic compounds bioavailability potential and they can be used as oral delivery systems.Livia de Souza Simoes gratefully acknowledges her grant to CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brasil) from Brazil. The authors also would like to acknowledge Luis Abrunhosa, from Centre of Biological Engineering, for assistance in High Pressure Liquid Chromatography -Fluorescence detection. This study was supported by FCT under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. This study was also supported by FCT under the scope of the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462).info:eu-repo/semantics/publishedVersio
Bio-based nanocarriers incorporating curcumin bioaccessibility and cell viability evaluation
Book of Abstracts of CEB Annual Meeting 2017[Excerpt] For decades, curcumin (Cur), a natural polyphenol product derived from turmeric (Curcuma longa) has been considered one of the most promising bioactive compounds due to its health benefits such as anti-inflammatory, antioxidant and anticarcinogenic properties. However, Cur application as functional compound in food products has been limited due to light, heat, and oxidation sensitive and mainly, to poor aqueous solubility which limit its bioavailability [1]. To increase Cur bioaccessibility and consequently, increase bioavailability, several carriers have been investigated, particularly nanocarriers. Among the various nanocarriers described in the literature, lipid-based nanocarriers may offer a promising tool to increase the stability, efficacy and safety of lipophilic compounds, namely Cur [2]. Moreover, the understanding of Cur-loaded nanocarriersâ behaviour under gastrointestinal (GI) conditions is fundamental to produce safe and customized nanocarriers with optimized bioactivity for oral consumption. The aim of this study was to comparatively analyze the impact of two different lipid nanocarriers incorporating Cur - solid lipid nanoparticles (SLN) and nanoemulsions (NE) â on bioaccessibility and Caco-2 cells viability. [...]info:eu-repo/semantics/publishedVersio
Regulation of Oxygen Distribution in Tissues by Endothelial Nitric Oxide
Nitric oxide (NO) decreases cellular oxygen (O2) consumption by competitively inhibiting cytochrome c oxidase. Here, we show that endogenously released endothelial NO, either basal or stimulated, can modulate O2 consumption both throughout the thickness of conductance vessels and in the microcirculation. Furthermore, we have shown that such modulation regulates O2 distribution to the surrounding tissues. We have demonstrated these effects by measuring O2 consumption in blood vessels in a hypoxic chamber and O2 distribution in the microcirculation using the fluorescent oxygen-probe Ru(phen)3^2+. Removal of NO by physical or pharmacological means, or in eNOS^ÂŻ/ÂŻ mice, abolishes this regulatory mechanism. Our results indicate that, in addition to its well-known effect on the regulation of vascular tone, endothelial NO plays a major role in facilitating the distribution of O2, an action which is crucial for the adaptation of tissues, including the vessel wall itself, to hypoxia. It is possible that changes in the distribution of O2 throughout the vessel wall may be implicated in the origin of vascular pathologies such as atherosclerosis.Victor Gonzalez, Victor Manuel, [email protected] ; d'Ocon Navaza, Maria Pilar, [email protected] ; Esplugues Mota, Juan Vicente, [email protected]
Advances in nutraceutical delivery systems: From formulation design for bioavailability enhancement to efficacy and safety evaluation
Background: Aiming at the enhancement of food products' nutritional and health value, the incorporation of nutraceuticals has attracted increasing interest in the last years. However, they often exhibit low water solubility and stability, limiting their direct incorporation into food products. Also, they show very low bioavailability due to limited bioaccessibility, poor absorption and/or chemical transformation within the gastrointestinal tract. This renders their health benefits extremely difficult to be realized by the consumers.
Scope and Approach
In the present review the recent innovations regarding the formulation and design of bio-based micro and nano-delivery systems to encapsulate nutraceuticals is discussed; it also gives an overview of the challenges associated to their development; and highlights some strategies to enhance nutraceuticals' bioavailability. An insight about delivery systems' potential toxicity (in particular at nano-scale) is also provided.
Key Findings and Conclusions
Recent developments in the design of bio-based delivery systems offer the possibility of stabilizing and enhancing nutraceuticals' functionality within food products. In fact, different strategies can be used to enhance nutraceuticals' bioavailability: i) nano-delivery systems, besides showing a huge potential for the protection of valuable nutraceuticals during food processing/digestion, can be used to increase their bioavailability; ii) absorption enhancement technologies have been successfully used to increase nutraceuticals' membrane permeation; and iii) excipient foods have been shown to improve nutraceuticals' biological activity. However, the application of these enabling technologies to food is hindered by very pertinent issues that can be summarized in the effective preservation/maximization of the nutraceuticals' bioactivity and safety, once inside the human body.Ana C. Pinheiro and Joana T. Martins acknowledge the Foundation for Science and Technology (FCT) for their fellowships (SFRH/BPD/ 101181/2014 and SFRH/BPD/89992/2012). This work was supported by Portuguese Foundation for Science and Technology (FCT) under the scope of the Project PTDC/AGR-TEC/5215/2014, of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-010145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio
Comparison of the optical quality vision between real post-LASIK myopic laser surgery and the simulated implantation of a phakic IOL in low myopia
A phakic intraocular lens (PIOL) ofâââ4.5 D was characterized from its wavefront aberration profile. A preclinical study was conducted using pre- and post-surgery data from four patients that had undergone myopic laser refractive surgery. All these patients would have needed a PIOL ofâââ4.5 D. Pre-surgery data were used to simulate the effect of a PIOL implantation. Post myopic refractive surgery data were used to calculate the post-LASIK eye model. Modulation transfer function (MTF), point spread function (PSF) and simulation of optotypes vision were obtained and compared. The PIOL did not worsen the optical quality of the eyes evaluated. High order Aberrations were always higher in the post-LASIK eye model. Optics quality trended to be better in PIOL implantation than post-LASIK surgery as pupil size increased.This work was supported by the âGeneralitat Valencianaâ of Spain (project AICO/2021/130)
Modeling anti-IL-6 therapy using breast cancer patient-derived xenografts
The pleiotropic cytokine IL-6 accelerates the progression of breast cancer in a variety of preclinical models through the activation of the STAT3 (signal transducer and activator of transcription 3) signaling pathway. However, the proportion of breast cancers sensitive to anti-IL-6 therapies is not known. This study evaluates the efficacy of anti-IL-6 therapies using breast cancer patient derived xenografts (PDXs). During the generation of our collection of PDXs, we showed that the successful engraftment of tumor tissue in immunodeficient mice correlates with bad prognosis. Four PDXs out of six were resistant to anti-IL-6 therapies and the expression of IL-6, its receptor or the levels of phospho-STAT3 (the active form of the signal transducer) did not correlate with sensitivity. Using cell cultures established from the PDXs as well as samples from in vivo treatments, we showed that only tumors in which the activation of STAT3 depends on IL-6 respond to the blocking antibodies. Our results indicate that only a fraction of breast tumors are responsive to anti-IL-6 therapies. In order to identify responsive tumors, a functional assay to determine the dependence of STAT3 activation on IL-6 should be performed
Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance
CĂĄncer de mama y de ovario; InhibiciĂłn WEE1CĂ ncer de mama i d'ovari; InhibiciĂł WEE1Breast and ovarian cancer; WEE1 inhibitionPurpose:
PARP inhibitors (PARPi) induce synthetic lethality in homologous recombination repair (HRR)-deficient tumors and are used to treat breast, ovarian, pancreatic, and prostate cancers. Multiple PARPi resistance mechanisms exist, most resulting in restoration of HRR and protection of stalled replication forks. ATR inhibition was highlighted as a unique approach to reverse both aspects of resistance. Recently, however, a PARPi/WEE1 inhibitor (WEE1i) combination demonstrated enhanced antitumor activity associated with the induction of replication stress, suggesting another approach to tackling PARPi resistance.
Experimental Design:
We analyzed breast and ovarian patient-derived xenoimplant models resistant to PARPi to quantify WEE1i and ATR inhibitor (ATRi) responses as single agents and in combination with PARPi. Biomarker analysis was conducted at the genetic and protein level. Metabolite analysis by mass spectrometry and nucleoside rescue experiments ex vivo were also conducted in patient-derived models.
Results:
Although WEE1i response was linked to markers of replication stress, including STK11/RB1 and phospho-RPA, ATRi response associated with ATM mutation. When combined with olaparib, WEE1i could be differentiated from the ATRi/olaparib combination, providing distinct therapeutic strategies to overcome PARPi resistance by targeting the replication stress response. Mechanistically, WEE1i sensitivity was associated with shortage of the dNTP pool and a concomitant increase in replication stress.
Conclusions:
Targeting the replication stress response is a valid therapeutic option to overcome PARPi resistance including tumors without an underlying HRR deficiency. These preclinical insights are now being tested in several clinical trials where the PARPi is administered with either the WEE1i or the ATRi.This work was supported by the Spanish Instituto de Salud Carlos III (ISCIII), an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds (FIS PI17/01080 to V. Serra, PI12/02606 to J. BalmaĂąa); European Research Area-NET, Transcan-2 (AC15/00063), AsociaciĂłn EspaĂąola contra el CĂĄncer (AECC; LABAE16020PORTT), the Agència de GestiĂł d'Ajuts Universitaris i de Recerca (AGAUR; 2017 SGR 540), La MaratĂł TV3 (654/C/2019), and ERAPERMED2019â215 to V. Serra. We also acknowledge the GHD-Pink program, the FERO Foundation, and the Orozco Family for supporting this study (to V. Serra). V. Serra was supported by the Miguel Servet Program (ISCIII; CPII19/00033); M. Castroviejo-Bermejo and C. Cruz (AIOC15152806CRUZ) by AECC; A. Herencia-Ropero by Generalitat de Catalunya-PERIS (SLT017/20/000081); M. Palafox by Juan de la Cierva (FJCI-2015â25412); A. Lau by AECC and Generalitat de Catalunya-PERIS (INVES20095LLOP, SLT002/16/00477); A. Gris-Oliver by FI-AGAUR (2015 FI_B 01075). This work was supported by Breast Cancer Research Foundation (BCRF-19â08), Instituto de Salud Carlos III Project Reference number AC15/00062, and the EC under the framework of the ERA-NET TRANSCAN-2 initiative co-financed by FEDER, Instituto de Salud Carlos III (CB16/12/00449 and PI19/01181), and AsociacioĚn EspanĚola Contra el CaĚncer (to J. Arribas). The xenograft program in the Caldas laboratory was supported by Cancer Research UK and also received funding from an EU H2020 Network of Excellence (EuroCAN). The RPPA facility is funded by NCI #CA16672
Generating and measuring the anisotropic elastic behaviour of Co thin films with oriented surface nano-strings on micro-cantilevers
In this research, the elastic behaviour of two Co thin films simultaneously deposited in an off-normal angle method was studied. Towards this end, two Si micro-cantilevers were simultaneously coated using pulsed laser deposition at an oblique angle, creating a Co nano-string surface morphology with a predetermined orientation. The selected position of each micro-cantilever during the coating process created longitudinal or transverse nano-strings. The anisotropic elastic behaviour of these Co films was determined by measuring the changes that took place in the resonant frequency of each micro-cantilever after this process of creating differently oriented plasma coatings had been completed. This differential procedure allowed us to determine the difference between the Young's modulus of the different films based on the different direction of the nano-strings. This difference was determined to be, at least, the 20% of the Young's modulus of the bulk Co
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