Genome-edited adult stem cells: Next-generation advanced therapy medicinal products

Over recent decades, gene therapy, which has enabled the treatment of several incurable diseases, has undergone a veritable revolution. Cell therapy has also seen major advances in the treatment of various diseases, particularly through the use of adult stem cells (ASCs). The combination of gene and cell therapy (GCT) has opened up new opportunities to improve advanced therapy medicinal products for the treatment of several diseases. Despite the considerable potential of GCT, the use of retroviral vectors has major limitations with regard to oncogene transactivation and the lack of physiological expression. Recently, gene therapists have focused on genome editing (GE) technologies as an alternative strategy. In this review, we discuss the potential benefits of using GE technologies to improve GCT approaches based on ASCs. We will begin with a brief summary of different GE platforms and techniques and will then focus on key therapeutic approaches that have been successfully used to treat diseases in animal models. Finally, we discuss whether ASC GE could become a real alternative to retroviral vectors in a GCT setting.European Regional Development Fund (FEDER), Grant/Award Numbers: PI18/01610, PI18/00330, PI18/00337, grants PI12/01097; Spanish ISCIII Health Research Fun

Valorization of CO2 through the Synthesis of Cyclic Carbonates Catalyzed by ZIFs

One way to exploit CO2 is to use it as a feedstock for the production of cyclic carbonates via its reaction with organic epoxides. As far as we know, there is still no heterogeneous catalyst that accelerates the reaction in a selective, efficient and industrially usable way. Cobalt and zinc-based zeolitic imidazole frameworks (ZIFs) have been explored as heterogeneous catalysts for this reaction. In particular, we have prepared ZIF-8 and ZIF-67 catalysts, which have been modified by partial replacement of 2-methylimidazole by 1,2,4-triazole, in order to introduce uncoordinated nitrogen groups with the metal. The catalysts have shown very good catalytic performance, within the best of the heterogeneous catalysts tested in the cycloaddition of CO2 with epichlorohydrin. The catalytic activity is due ultimately to defects on the outer surface of the crystal, and varies in the order of ZIF-67-m > ZIF-67 > ZiF-8-m = ZIF-8. Notably, reactions take place under mild reaction conditions and without the use of co-catalysts.The authors acknowledge financial support by MINECO (Spain) through the projects MAT2017-86992-R and CTQ2017-88171-P, “Ministerio de Ciencia e innovación” (PID2020-116998RB-I00), Ministerio de Educación y Formación Profesional (PRX21/00407), and Conselleria de Innovacion, Universidades, Ciencia y Sociedad Digital (CIPROM/2021/022, MFA/2022/048)

Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging

The aim of this review is to explore the relationship between melatonin, free radicals, and non-excitatory amino acids, and their role in stroke and aging. Melatonin has garnered significant attention in recent years due to its diverse physiological functions and potential therapeutic benefits by reducing oxidative stress, inflammation, and apoptosis. Melatonin has been found to mitigate ischemic brain damage caused by stroke. By scavenging free radicals and reducing oxidative damage, melatonin may help slow down the aging process and protect against age-related cognitive decline. Additionally, non-excitatory amino acids have been shown to possess neuroprotective properties, including antioxidant and anti-inflammatory in stroke and aging-related conditions. They can attenuate oxidative stress, modulate calcium homeostasis, and inhibit apoptosis, thereby safeguarding neurons against damage induced by stroke and aging processes. The intracellular accumulation of certain non-excitatory amino acids could promote harmful effects during hypoxia-ischemia episodes and thus, the blockade of the amino acid transporters involved in the process could be an alternative therapeutic strategy to reduce ischemic damage. On the other hand, the accumulation of free radicals, specifically mitochondrial reactive oxygen and nitrogen species, accelerates cellular senescence and contributes to age-related decline. Recent research suggests a complex interplay between melatonin, free radicals, and non-excitatory amino acids in stroke and aging. The neuroprotective actions of melatonin and non-excitatory amino acids converge on multiple pathways, including the regulation of calcium homeostasis, modulation of apoptosis, and reduction of inflammation. These mechanisms collectively contribute to the preservation of neuronal integrity and functions, making them promising targets for therapeutic interventions in stroke and age-related disorders.This work was supported by MICIU (grant number PID2021-128133NB-I00/AEI/FEDER10.13039/501100011033) to J.M.H.-G. and V.J.C. enjoys a contract from the CAM “Investigo” program (PIP/2022-09971). A.R. thanks UCJC (INFLAMAMEL 2022-07 project) for its continued support

Social perception of the salinization of water for domestic use in Puerto Madero, Chiapas, México

[EN] The salinization of drinking water in the coastal zone is a growing concern for water security. Our objective was to know the perception of water salinization for domestic use through semistructured interviews in Puerto Madero, Mexico, a border community with high levels of migration, and then to contrast it with quantitative salinity data. The population of this coastal locality depends substantially on artisan wells without government monitoring. Although no wells were classified as saline, results show that artisan wells that present extreme values of dissolved-solid concentration have impact in human health conditions.[ES] La salinización del agua potable en la zona costera representa una creciente preocupación de la seguridad hídrica. Nuestro objetivo fue explorar, a través de entrevistas semiestructuradas, la percepción de la salinización del agua para uso doméstico en Puerto Madero, México, una comunidad fronteriza con altos niveles de migración, y contrastarla con datos cuantitativos de salinidad. La población de esta localidad costera depende sustancialmente de pozos artesanales sin monitoreo gubernamental. Aunque no se encontraron pozos que puedan catalogarse como salinos, los resultados evidencian que los pozos artesanos que presentan valores extremos de concentración de sólidos disueltos tienen incidencia en la salud humana.Los autores agradecen al Consejo Nacional de Ciencia y Tecnología por la beca otorgada para estudios de posgrado, al Laboratorio Transdisciplinario para la Sustentabilidad (LATSU) de ECOSUR por el espacio de colaboración y discusión facilitado, a la Lic. C. Robledo por el apoyo en la formulación de la entrevista, al Mtro. F.J. Valle Mora por las recomendaciones en el análisis estadístico, a G.M. Williams Jara por la elaboración del mapa de localización del área de estudio, y a M. Hernández por la revisión de estilo.Barrios-Ramos, I.; Espinoza-Tenorio, A.; Mesa-Jurado, MA.; Tovilla-Hernández, C.; Mendoza-Carranza, M. (2021). Percepción social de la salinización del agua para uso doméstico en Puerto Madero, Chiapas, México. Economía Agraria y Recursos Naturales - Agricultural and Resource Economics. 21(1):7-34. https://doi.org/10.7201/earn.2021.01.01OJS73421

Isogenic GAA-KO Murine Muscle Cell Lines Mimicking Severe Pompe Mutations as Preclinical Models for the Screening of Potential Gene Therapy Strategies

Pompe disease (PD) is a rare disorder caused by mutations in the acid alpha-glucosidase (GAA) gene. Most gene therapies (GT) partially rely on the cross-correction of unmodified cells through the uptake of the GAA enzyme secreted by corrected cells. In the present study, we generated isogenic murine GAA-KO cell lines resembling severe mutations from Pompe patients. All of the generated GAA-KO cells lacked GAA activity and presented an increased autophagy and increased glycogen content by means of myotube differentiation as well as the downregulation of mannose 6-phosphate receptors (CI-MPRs), validating them as models for PD. Additionally, different chimeric murine GAA proteins (IFG, IFLG and 2G) were designed with the aim to improve their therapeutic activity. Phenotypic rescue analyses using lentiviral vectors point to IFG chimera as the best candidate in restoring GAA activity, normalising the autophagic marker p62 and surface levels of CI-MPRs. Interestingly, in vivo administration of liver-directed AAVs expressing the chimeras further confirmed the good behaviour of IFG, achieving cross-correction in heart tissue. In summary, we generated different isogenic murine muscle cell lines mimicking the severe PD phenotype, as well as validating their applicability as preclinical models in order to reduce animal experimentation.Fundacion Poco Frecuente (Almeria)Asociacion Espanola de Enfermos de Glucogenosis (AEEG)Asociacion Espanola de Enfermos de Pompe (AEEP

Co-creation Initiatives in Healthcare in Small Communities

The uses of technology in public spaces are not new, but now we find new forms of social interactions and practices, socio-spatial representations and relationships. The close relationship between real and virtual worlds also opens up new ways of advancing knowledge. In order to facilitate the implementation of Open Science, we explore different co-creation methods with multiple stakeholders. All groups are involved and have influence throughout the project lifecycle: from the beginning, to planning, to implementation, to dissemination. Research activities should involve a wide variety of stakeholders interested, including government, educators, nurses, charities, civil societies, patient groups and the publics, based in a way to (1) obtaining contributions by customers, (2) selecting the best of these contributions, and (3) incorporating these selected contributions into products, processes, or services. Interactions between Information and Communication Technologies (ICT), public spaces, and healthcare are considered as s a tool for connecting people in small communities (enhancing participation). A Platform (DXP - Digital eXperience Platform) through “headless” technologies may provide content management capabilities and easy integration with devices and various sources, driven by user needs and developed with the concept of “Community in mind” in order to create strong and active communities and transform our small communities into more human environments, rather than just more high-tech places, and to understand that “smartness” should be people-friendly. It was applies the Responsible Research and Innovation (RRI) principles on the scientific process and governance, identify drivers and barriers, interests and values for current and future societal challenges.This research was financially supported by the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 741527 (project ORION).S

Caracterización magnética de polvo urbano y plantas de la Zona Metropolitana del Valle de México

"Investigaciones recientes han demostrado que los gases automotores contienen elementos potencialmente tóxicos, los cuales se acumulan sobre las superficies del suelo urbano (asfalto, cemento, empedrado, etc.) y se mezclan con el polvo urbano (PU). En este estudio se determinan los valores de umbrales magnéticos por medio de muestras de PU depositado en calles y hojas de plantas provenientes de zonas con diferentes tipos de usos del suelo de la Zona Metropolitana del Valle de México. Se colectaron 89 muestras de PU y un mismo número de muestras de hojas de Ficus benjamina de zonas con diferentes tipos de uso de suelo (habitacional, equipamiento, habitacional-comercial, espacios abiertos e industria). Los parámetros magnéticos determinados fueron: susceptibilidad magnética específica másica (χlf), porcentaje de la susceptibilidad dependiente de la frecuencia (χdf%), magnetización remanente isotermal a 700 mT (MRI0.7) y adicionalmente la concentración de Pb y Zn. Las curvas de magnetización vs campo magnético presentaron una saturación de la magnetización para campos magnéticos entre 200 a 300 mT y la fracción S-200 (S-200 = MRI-0.2/MRI0.7) presentó valores entre 0.7 a 1.0; este comportamiento es característico de muestras con minerales de baja coercitividad magnética (ferrimagnéticos). Las curvas termomagnéticas (κ vs T) de PU indican que la principal fase magnética es alrededor de 580 °C, lo que sugiere la presencia de titano-magnetita pobre en Ti y magnetita. Las concentraciones de Pb y Zn presentan correlación estadísticamente aceptable con los parámetros magnéticos. Los análisis discriminantes en ambos tipos de muestras (agrupación por tipos de uso del suelo, las variables χlf, χdf%, MRI0.7 y las concentraciones de Pb y Zn) dan un resultado menor al 50% en ambos casos. Por tanto, no es posible establecer diferencias significativas entre los tipos de uso de suelo, los parámetros magnéticos medidos y la concentración de Pb y Zn. La determinación de los valores umbrales magnéticos se obtuvo del polvo urbano con las menores concentraciones de Pb y Zn. Los valores umbrales para el PU fueron: MRI0.7 = 58 mAm2 kg-1 y χlf = 4.5 mm3 kg-1, en tanto que para las plantas fueron: MRI0.7 = 1.6 mAm2 kg-1 y χlf = 0.13 mm3 kg-1. Las representaciones espaciales de los valores umbrales de MRI0.7 de PU y plantas revelaron que las zonas de la parte central y sureste de la Zona Metropolitana del Valle de México son potencialmente peligrosas por su alta concentración de Pb o Zn.""Recent investigations have demonstrated that motor-vehicle gas contains particles with potentially toxic elements. These contaminating particles accumulate on the soil surface or overlying material (asphalt, stone and concrete pavements) and they are usually mixed with urban dust. In this work we determine the magnetic threshold values using urban dust and leave samples collected from different type of urban land-use soil along the metropolitan area of Mexico City and identify potentially dangerous areas considering potentially toxic elements. 89 urban dust samples deposited on the streets and same number of Ficus benjamina leaves were collected from different land-use zones (residential, equipment, residentialcommercial, open space and industry). The magnetic parameters determined were: mass especific magnetic susceptibility (χ lf), percentage frequency dependent susceptibility (χ df%), isothermal remanent magnetization at 700 mT (IRM0.7). Additionally the concentrations of Pb and Zn were also obtained. Isothermal remanence acquisition curves for dust samples yielded a saturation between 200 and 300 mT and S-200 (S-200= MRI-0.2/MRI0.7) fraction values were found between 0.7 to 1.0 - characteristic of samples with low magnetic coercivity minerals (ferrimagnetics). The κ vs T curves indicate the main magnetic phase about 580 °C which attests the presence of Ti-poor titanomagnetite or almost pure magnetite. The Pb and Zn concentrations show acceptable statistically correlation with magnetic parameters. Discriminant analyzes in both types of samples gave values low than 50% in both cases. Therefore, it is not possible to attest the significant differences between measured magnetic parameters, concentration of Pb and Zn and soil type. The threshold values for urban dust were MRI0.7 = 58 mAm2 kg-1 and χlf = 4.5 mm3 kg-1 while the plant threshold values were: MRI0.7 = 1.6 mAm2 kg-1 and χlf = 0.13 mm3 kg-1. Spatial representations of these threshold values revealed that zones from central and southeast of Valle de Mexico Metropolitan Zone are the most potentially dangerous areas considering their high concentration of Pb and Zn.

EDUCACIÓN AMBIENTAL Y SOCIEDAD. SABERES LOCALES PARA EL DESARROLLO Y LA SUSTENTABILIDAD

Este texto contribuye al análisis científico de varias áreas del conocimiento como la filosofía social, la patología, la educación para el cuidado del medio ambiente y la sustentabilidad que inciden en diversas unidades de aprendizaje de la Licenciatura en Educación para la Salud y de la Maestría en Sociología de la SaludLas comunidades indígenas de la sierra norte de Oaxaca México, habitan un territorio extenso de biodiversidad. Sin que sea una área protegida y sustentable, la propia naturaleza de la región ofrece a sus visitantes la riqueza de la vegetación caracterizada por sus especies endémicas que componen un paisaje de suma belleza