Development of Hybrid Nanoplatforms for Theranostic Applications

There is a need of new approaches in which cancer and other diseases are adressed. These new methods must be capable to reduce doses, treatment times, and damage to healty tissues. Furthermore, it is desirable that these systems function as diagnosis and imaging agents, so the evolution of the disease can be visualized in real time and decisions about treatment regimes can be made as soon as possible. The combination of therapeutic and diagnostic/imaging agents in one system creates a new concept called theranostics; hence, a theranostic system can treat the disease and, at the same time, work as a diagnostic and imaging agent. The objective of this thesis has been the synthesis, characterization and evaluation of different multifunctional theranostic nanoplatforms that can be applied in cancer treatment, diagnosis and imaging. The processes used to prepare them have involved low energy consumption and most of the materials were biocompatible. The results obtained from their physicochemical characterization and performance in vitro and in vivo suggest that these nanoplatforms could be used as anticancer treatments with more effective results, allowing lower doses, treatment times, and combined therapies applied locally and simultaneously

Water and its legislation. Agreements and conflicts in the Central Valleys of Oaxaca (México), in the transition from the nineteenth to the twentieth century

Se considera que las leyes, decretos y bandos influían o marcaban normas en las sociedades rurales y urbanas; lo cual es parcialmente cierto. Sin embargo, poco se ha analizado cómo esas leyes se nutren de las normas y derechos ejercidas por diversos actores sociales, y cómo a su vez fueron utilizadas en las tensiones sociales. En este artículo, mostramos cómo en los Valles Centrales de Oaxaca, los diversos actores sociales se ajustaron o pretendieron modificar su acceso, manejo, control y administración del agua en la transición del siglo XIX al siglo XX.Laws, decrees and sides are considered to influence or set standards in rural and urban societies; which is partially true. However, little has been analyzed how these laws are based on the norms and rights exercised by various social actors, and how they were in turn used in social tensions. In this article, we show how in the Central Valleys of Oaxaca, the various social actors adjusted or intended to modify their access, management, control and water management in the transition from the nineteenth to the twentieth century.Instituto de Investigaciones en Humanidades y Ciencias Sociale

Proyecto de desarrollo de modelo de negocio Mercado Verde

Se plantea un modelo de negocio web/móvil que permita al segmento de mercado hombres y mujeres de 30 a 45 años de edad comprar y recibir productos naturales de manera conveniente. La idea es conseguir productores de calidad para una cantidad limitada de productos identificados como estratégicos, para partir de ahí como base y comenzar a ofrecerlos mediante medios digitales, para esto se generó una landing page página de aterrizaje (una página web diseñada específicamente para convertir visitantes en leads) que nos ayude a capturar clientes potenciales, así como información de ellos sobre los productos estratégicos. Toda esta propuesta se ha ido consolidando a través de más de 90 entrevistas presenciales con clientes potenciales, en donde semana a semana se hace una consolidación de la información en búsqueda de los hallazgos más relevantes, para a partir de ahí modificar si es necesario el modelo de negocio, pero también las entrevistas. También se ha medido la respuesta del mercado a través de la utilización de la landing page, con la cual se obtuvo una base de datos de 185 clientes potenciales con los cuales se está interactuando para consolidarlos como clientes reales y posteriormente como suscriptores.ITESO, A.C

Inhibiting HER3 Hyperphosphorylation in HER2‐Overexpressing Breast Cancer through Multimodal Therapy with Branched Gold Nanoshells

Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+/HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrierE.V.-A. and I.G.-C. contributed equally to this work. This work was sup ported by the Agencia Estatal de Investigación (AEI) through Project No. PID2019-109517RB-I00) and from the Xunta de Galicia, Project No. ED431C2022/18. European Regional Development Funds are also ac knowledged. A.A.-M. and P.T. also thank the International Scientific Part nership Program ISSP at King Saud University for additional funding of this research through Grant No. ISPP-144. This work also received fi nancial support from the ISCIII, Ministerio de Economía y Competitivi dad (Grant No. PI15/01129; J.A.C.), and the AEI (Grant No. PID2020- 113501RB-I00; J.A.C.). I.-G.C. thanks for financial support through Grant No. PRE/2011/131, and the Centro Singular de Investigación de Galicia accreditation Grant No. 2016–2019 ED431G/05)S

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.This study has been partially supported by grants from Axencia Galega de Innovación (Xunta de Galicia), the Instituto de Salud Carlos III (PI13/00292; PI14/01879), the Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS (RD12/0014), Xunta de Galicia (Consellería Educación GRC2014/027), the European Commission program FEDER and Promoting Active Ageing program: Functional Nanostructures For Alzheimer’s Disease At Ultra-Early Stages” (Pana_686009), a Research and Innovation Project, funded within the EU Horizon 2020 Programme”. Furthermore, this study was also co-funded within the POCTEP (Operational Programme for Cross-border Cooperation Spain-Portugal) program (0681_INVENNTA_1_E), co-financed by the ERDF (European Regional Development Fund). T. Sobrino (CP12/03121) and F. Campos (CP14/00154) are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos III. Finally, P. Taboada thanks Mineco and Xunta de Galicia for funding through projects MAT2013-40971-R and EM2013-046, respectively. J Trekker is the recipient of an innovation grant from the IWT-VlaanderenS

La nueva gerencia pública como limitante de la mediación transformativa en México

The objective of this article was to analyze the figure on the new public management and its impact on the transformative model of mediation. For it, the deductive, documentary, discursive, legal systematic and functionalist methods were used. The results indicate that the axis called accountability —by focusing its study in quantitative statistical terms, but not qualitative— forces mediation centers in judicial headquarters to prioritize the generation of statistics on signed agreements over the transformation of behavior of the part mediated, which has a negative impact on the transformative model and the non-recidivism in conflicts. The most important limitation was the obtaining of specific statistical data on the number of cases presented and agreements signed before the mediation centers, the main finding of the study being, in the sense that the Mexican State uses the classic mediation model, which it focuses on obtaining an agreement between the parts, thereby sustaining a policy of reaction that is increasingly moving away from the policy of conflict prevention. This situation serves to conclude that the policy of the new public management in the mediation centers of judicial headquarters should be eliminated to give them the opportunity to use the transformative method for conflict resolution. The hypothetical assumption of this article consisted in substantiate the need to apply the transformative model for mediation within the judiciary in Mexico; However, the ideology of the New public management that the Mexican State has implemented greatly hinders the benefits and scope of conflict prevention and non-repetition of the facts, so it is necessary to cease the operation of mediation based on the principles of the new public management so that the aims of transformative mediation can be adoptedO objetivo deste artigo foi analisar a figura da nova gestão pública e seu impacto no modelo transformador de mediação. Para tanto, foram utilizados os métodos dedutivo, documental, discursivo, sistemático jurídico e funcionalista. Os resultados indicam que o eixo denominado accountability - por focar seu estudo em termos estatísticos quantitativos, mas não qualitativos - obriga os centros de mediação nas sedes judiciais a priorizar a geração de estatísticas sobre acordos firmados em detrimento da transformação de comportamento do meio, o que impacta negativamente o modelo transformador e a não reincidência em conflitos. A limitação mais importante foi a obtenção de dados estatísticos específicos sobre o número de casos apresentados e acordos firmados junto aos centros de mediação, sendo o principal achado do estudo, no sentido de que o Estado mexicano utiliza o modelo clássico de mensuração, que centra-se na obtenção de um acordo entre as partes, sustentando assim uma política de reação que se distancia cada vez mais da política de prevenção de conflitos. Esta situação permite concluir que a política da nova gestão pública nos centros de mediação das sedes judiciais deve ser eliminada para lhes dar a oportunidade de utilizar o método transformador de resolução de conflitos. O pressuposto hipotético deste artigo consistiu em fundamentar a necessidade de aplicar o modelo transformador de mediação no Poder Judiciário mexicano; No entanto, a ideologia da nova gestão pública que o Estado mexicano tem implementado dificulta sobremaneira os benefícios e alcance da prevenção de conflitos e da não repetição dos eventos, por isso é necessário cessar a operação de mediação com base no princípios da nova gestão pública para que os objetivos da mediação transformadora possam ser adotados.El objetivo del presente artículo fue analizar la figura sobre la nueva gerencia pública y su impacto en el modelo transformativo de la mediación. Para ello, se usaron los métodos deductivo, documental, discursivo, sistemático jurídico y funcionalista. Los resultados señalan que el eje denominado rendición de cuentas —al focalizar su estudio en términos estadísticos cuantitativos, mas no cualitativos— obliga a los centros de mediación en sede judicial a priorizar la generación de estadísticas sobre acuerdos firmados por encima de la transformación de la conducta de los mediados, lo que impacta de forma negativa en el modelo transformativo y en la no reincidencia en los conflictos. La limitación más importante fue la obtención de datos estadísticos específicos sobre el número de asuntos presentados y acuerdos signados ante los centros de mediación, siendo el principal hallazgo del estudio, en el sentido de que el Estado mexicano utiliza el modelo clásico de medición, el cual se centra en la obtención de un acuerdo entre las partes, con lo que se sostiene una política de reacción que se aleja cada vez más de la política de prevención del conflicto. Esta situación sirve para concluir que se debe eliminar la política de la nueva gerencia pública en los centros de mediación de sede judicial para brindarles la oportunidad de utilizar el método transformativo para la resolución de conflictos. El supuesto hipotético del presente artículo consistió en fundamentar la necesidad de aplicar el modelo transformativo para la mediación dentro del Poder Judicial en México; sin embargo, la ideología de la nueva gerencia pública que ha implementado el Estado mexicano dificulta en gran medida los beneficios y alcances de prevención de conflictos y no repetición de los hechos, por lo que es necesario cesar el funcionamiento de la mediación con base en los principios de la nueva gerencia pública para que se puedan adoptar los fines de la mediación transformativ

El agua y su legislación. Acuerdos y conflictos en los Valles Centrales de Oaxaca (México), en la transición del siglo XIX al siglo XX

Laws, decrees and sides are considered to influence or set standards in rural and urban societies; which is partially true. However, little has been analyzed how these laws are based on the norms and rights exercised by various social actors, and how they were in turn used in social tensions. In this article, we show how in the Central Valleys of Oaxaca, the various social actors adjusted or intended to modify their access, management, control and water management in the transition from the nineteenth to the twentieth century.Se considera que las leyes, decretos y bandos influí­an o marcaban normas en las sociedades rurales y urbanas; lo cual es parcialmente cierto. Sin embargo, poco se ha analizado cómo esas leyes se nutren de las normas y derechos ejercidas por diversos actores sociales, y cómo a su vez fueron utilizadas en las tensiones sociales. En este artí­culo, mostramos cómo en los Valles Centrales de Oaxaca, los diversos actores sociales se ajustaron o pretendieron modificar su acceso, manejo, control y administración del agua en la transición del siglo XIX al siglo XX

Migración jornalera agrícola en la caña de azúcar en Nayarit, México

The objective of this article is to describe the migratory phenomenon associated to the sugar cane cultivation in the state of Nayarit, the migratory routes, migrants profiles, and, with those, an approximation of their life conditions in the differents places of destination. To the gathering of information, it was used the cualitative methodology. With the analysis we found that: a) Life conditions of the destination places in the cane zone of  Nayarit, still being precarious, they’re perceived by the cane workers as better as their native (origin) places by the health access and the weather conditions that aloud “to give up¨ the work and therefore the incomes obtained by  it; b) The migratory routes are diverse, traditionally south-north, but it also exists the non traditional ¨north-south¨ and; c) the presence of the work at the plots, machete in hand, of woman cutting the cane.El objetivo del artículo es describir el fenómeno migratorio asociado al cultivo de la caña en el estado de Nayarit, las rutas migratorias, perfiles de los migrantes y, con ellos, una aproximación a sus condiciones de vida en lugares de destino. Para la recolección de información se utilizó básicamente metodología cualitativa. Con el análisis encontramos que: a) las condiciones de vida en los lugares de destino en la zona cañera de Nayarit, aún siendo precarias, son percibidas por los cortadores como mejores a las de su lugar de origen por el acceso a servicios de salud y las condiciones climáticas que permiten “hacer rendir” el trabajo y por ende los ingresos obtenidos por él; b) las rutas migratorias son diversas, tradicionalmente sur-norte, pero también existen las no tradicionales “norte-sur” y; c) la presencia del trabajo en las parcelas, machete en mano, de las mujeres cortando caña