Nanoparticle-based immunotherapeutics: from the properties of nanocores to the differential effects of administration routes

The engagement with the immune system is one of the main cornerstones in the development of nanotechnologies for therapy and diagnostics. Recent advances have made possible the tuning of features like size, shape and biomolecular modifications that influence such interactions, however, the capabilities for immune modulation of nanoparticles are still not well defined and exploited. This review focuses on recent advances made in preclinical research for the application of nanoparticles to modulate immune responses, and the main features making them relevant for such applications. We review and discuss newest evidence in the field, which include in vivo experiments with an extensive physicochemical characterization as well as detailed study of the induced immune response. We emphasize the need of incorporating knowledge about immune response development and regulation in the design and application of nanoparticles, including the effect by parameters such as the administration route and the differential interactions with immune subsetsThe authors thank the financial support of the European Research Council (starting grant #950421), the European Union (INTERREG V-A Spain–Portugal #0624_2IQBIONEURO_6_E, NextGeneration EU/PRTR and ERDF; H2020-FET-Open grant agreement No. 899612), the MCIN/AEI (PID2020-119206RB-I00, PID2020-119479RA-I00, PID2019-111218RB-I00, RYC-2017-23457, RYC-2019-028238-I and RYC2021‐034576‐I), and the Xunta de Galicia (ED431F 2021/02, 2021-CP090, ED431C 2022/018, and Centro Singular De Investigación de Galicia Accreditation 2019–2022 #ED431G 2019/03). This project was also supported by the ISCIII, under the framework of EuroNanoMed III_2020 (AC20/00041, PLATMED)S

New Approaches in Nanomedicine for Ischemic Stroke

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in developed countries. Therapeutic methods such as recanalization approaches, neuroprotective drugs, or recovery strategies have been widely developed to improve the patient’s outcome; however, important limitations such as a narrow therapeutic window, the ability to reach brain targets, or drug side effects constitute some of the main aspects that limit the clinical applicability of the current treatments. Nanotechnology has emerged as a promising tool to overcome many of these drug limitations and improve the efficacy of treatments for neurological diseases such as stroke. The use of nanoparticles as a contrast agent or as drug carriers to a specific target are some of the most common approaches developed in nanomedicine for stroke. Throughout this review, we have summarized our experience of using nanotechnology tools for the study of stroke and the search for novel therapiesThis project was supported by the FRQS, ISCIII (AC19/00031 and AC20/00041), and ANR under the framework of EuroNanoMed III_2020 (PLATMED_project); the European Union program FEDER and the European Regional Development Fund–ERDF; and the Xunta de Galicia (IN607D2020/03 and ED431G2019/03). E.P. and B.P acknowledge the AEI grants (PID2019-111218RB-I00 and RyC-2017-23457). Finally, F.C. thanks the ISCIII and Miguel Servet program (CPII19/00020)S

Evaluation of multiple sclerosis severity using a new OCT tool

Purpose: To assess the ability of a new posterior pole protocol to detect areas with significant differences in retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness in patients with multiple sclerosis versus healthy control subjects; in addition, to assess the correlation between RNFL and GCL thickness, disease duration, and the Expanded Disability Status Scale (EDSS). Methods: We analyzed 66 eyes of healthy control subjects and 100 eyes of remitting-relapsing multiple sclerosis (RR-MS) patients. Double analysis based on first clinical symptom onset (CSO) and conversion to clinically definite MS (CDMS) was performed. The RR-MS group was divided into subgroups by CSO and CDMS year: CSO-1 (≤ 5 years) and CSO-2 (≥ 6 years), and CDMS-1 (≤ 5 years) and CDMS-2 (≥ 6 years). Results: Significant differences in RNFL and GCL thickness were found between the RR-MS group and the healthy controls and between the CSO and CDMS subgroups and in both layers. Moderate to strong correlations were found between RNFL and GCL thickness and CSO and CDMS. Furthermore, we observed a strong correlation with EDSS 1 year after the OCT examination. Conclusions: The posterior pole protocol is a useful tool for assessing MS and can reveal differences even in early stages of the disease. RNFL thickness shows a strong correlation with disability status, while GCL thickness correlates better with disease duration

High-yield halide-assisted synthesis of metal–organic framework UiO-based nanocarriers

The synthesis of nanosized metal–organic frameworks (NMOFs) is requisite for their application as injectable drug delivery systems (DDSs) and other biorelevant purposes. Herein, we have critically examined the role of different synthetic parameters leading to the production of UiO-66 crystals smaller than 100 nm. Of note, we demonstrate the co-modulator role conferred by halide ions, not only to produce NMOFs with precise morphology and size, but also to significantly improve the reaction yield. The resulting NMOFs are highly crystalline and exhibit sustained colloidal stability in different biologically relevant media. As a proof of concept, these NMOFs were loaded with Rhodamine 6G (R6G), which remained trapped in most common biologically relevant media. When incubated with living mammalian cells, the R6G-loaded NMOFs were efficiently internalized and did not impair cell viability even at relatively high doses.The authors acknowledge the financial support of the MCIN/AEI (PID2019-108624RB-I00, RYC-2017-23457, RYC-2019-028238-I), the Xunta de Galicia (ED431F 2017/02, ED431F 2020/11, 2021-CP090, Centro Singular de Investigación de Galicia Accreditation 2019–2022, ED431G 2019/03), the European Union (European RegionalDevelopment Fund – ERDF; H2020-MSCA-ITN grant agreement no. 860942; H2020-FET-Open grant agreement no. 899612; H2020-ICT grant agreement no. 10101694 and INTERREG V-A Spain–Portugal, project 0624_2IQBIONEURO_6_E), and the European Research Council (starting grant no. 950421). M.C.-M. thanks the AEI (FPU19/03155). The authors are grateful for the use of RIAIDT-USC analytical facilities.S

Desarrollo de formación complementaria y de apoyo a los estudios del Grado en Historia y Ciencias de la Música para la adquisición de herramientas básicas de lenguaje y análisis musical

Memoria ID-0042. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2017-2018

Hydrodynamics and electrical insulation of PbLi flow with SiC flow channel inserts in a strong magnetic field

Experimental and numerical research in a strong magnetic field is described in this article testing silicon carbide (SiC) flow channel inserts (FCI) in lead-lithium (PbLi) liquid metal flow. The study aims to further develop the High-Temperature Dual-Coolant Lead-Lithium nuclear fusion blanket concept by testing new variations of SiC inserts operating in the relevant electromagnetic conditions. These inserts act as electrical insulators in magnetohydrodynamic lead-lithium flow and can also play the role of the thermal insulator in the potentially real fusion environment. The liquid metal pressure and integral flowrate measurements were performed on up to 5T DC magnetic field created by a superconducting magnet at high temperatures up to 700 °C, which is close to the real fusion environment. Comparisons of several cases with and without inserts are provided, demonstrating their impact on hydraulic resistance. Additionally, electrical potential distribution is recorded on the lead-lithium channel walls, which can be used to evaluate the character of liquid metal velocity distribution in the lead-lithium channel

Mammographic density and breast cancer in women from high risk families

Introduction: Mammographic density (MD) is one of the strongest determinants of sporadic breast cancer (BC). In this study, we compared MD in BRCA1/2 mutation carriers and non-carriers from BRCA1/2 mutation-positive families and investigated the association between MD and BC among BRCA1/2 mutation carriers per type of mutation and tumor subtype. Methods: The study was carried out in 1039 female members of BRCA1 and BRCA2 mutation-positive families followed at 16 Spanish Genetic Counseling Units. Participants' density was scored retrospectively from available mammograms by a single blinded radiologist using a 5-category scale (75 %). In BC cases, we selected mammograms taken prior to diagnosis or from the contralateral breast, whereas, in non-cases, the last screening mammogram was evaluated. MD distribution in carriers and non-carriers was compared using ordinal logistic models, and the association between MD and BC in BRCA1/2 mutation carriers was studied using logistic regression. Huber-White robust estimators of variance were used to take into account correlations between family members. A similar multinomial model was used to explore this association by BC subtype. Results: We identified and scored mammograms from 341 BRCA1, 350 BRCA2 mutation carriers and 229 non-carriers. Compared to non-carriers, MD was significantly lower among BRCA2 mutation carriers (odds ratio (OR) =0.71; P-value=0.04), but not among BRCA1 carriers (OR=0.84; P-value=0.33). MD was associated with subsequent development BC (OR per category of MD=1.45; 95 % confidence interval=1.18-1.78, P-value<0.001), with no significant differences between BRCA1 and BRCA2 mutation carriers (P-value=0.48). Finally, no statistically significant differences were observed in the association of MD with specific BC subtypes. Conclusions: Our study, the largest to date on this issue, confirms that MD is an independent risk factor for all BC subtypes in either BRCA1 and BRCA2 mutation carriers, and should be considered a phenotype risk marker in this context

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