Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend the disease’s pathogenesis is crucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease’s pathological processes. Purpose: To identify the immune and nervous system-derived EV profile from blood that could have a specific role as biomarker in MS and assess its possible correlation with disease state. Results: Higher levels of T cell-derived EVs and smaller size of neuron-derived EVs were associated with clinical relapse. The smaller size of the oligodendrocyte-derived EVs was related with motor and cognitive impairment. The proteomic analysis identified mannose-binding lectin serine protease 1 and complement factor H from immune system cell-derived EVs as autoimmune disease-associated proteins. We observed hepatocyte growth factor-like protein in EVs from T cells and inter-alpha-trypsin inhibitor heavy chain 2 from neurons as white matter injury-related proteins. In patients with MS, a specific protein profile was found in the EVs, higher levels of alpha-1-microglobulin and fibrinogen β chain, lower levels of C1S and gelsolin in the immune system-released vesicles, and Talin-1 overexpression in oligodendrocyte EVs. These specific MS-associated proteins, as well as myelin basic protein in oligodendrocyte EVs, correlated with disease activity in the patients with MS. Conclusion: Neural-derived and immune-derived EVs found in blood appear to be good specific biomarkers in MSfor reflecting the disease stateWe greatly appreciate the support of Morote Traducciones S.L. for their editing assistance. This work was sponsored by a grant from Miguel Servet (CP20/00024 to Laura Otero-Ortega), Miguel Servet (CPII20/00002 to María Guti´errez-Fernández), a predoctoral fellowship (FI18/00026 to Fernando Laso-García), a Río-Hortega grant (CM22/00065 to Gabriel Torres Iglesias and CM20/00047 to Elisa Alonso-Lopez) and byResearch Project (PI21/00918) from the Instituto de Salud Carlos III and co-funded by the European Union and by a grant CA1/RSUE/2021-00753 to Dolores Piniella funded by Ministerio de Universidades, Plan de Recuperacion, ´ Transformacion ´ y Resiliencia y la Universidad Autónoma de Madri

The Effectiveness of Glutathione Redox Status as a Possible Tumor Marker in Colorectal Cancer

[EN] The role of oxidative stress (OS) in cancer is a matter of great interest due to the implication of reactive oxygen species (ROS) and their oxidation products in the initiation of tumorigenesis, its progression, and metastatic dissemination. Great efforts have been made to identify the mechanisms of ROS-induced carcinogenesis; however, the validation of OS byproducts as potential tumor markers (TMs) remains to be established. This interventional study included a total of 80 colorectal cancer (CRC) patients and 60 controls. By measuring reduced glutathione (GSH), its oxidized form (GSSG), and the glutathione redox state in terms of the GSSG/GSH ratio in the serum of CRC patients, we identified significant changes as compared to healthy subjects. These findings are compatible with the effectiveness of glutathione as a TM. The thiol redox state showed a significant increase towards oxidation in the CRC group and correlated significantly with both the tumor state and the clinical evolution. The sensitivity and specificity of serum glutathione levels are far above those of the classical TMs CEA and CA19.9. We conclude that the GSSG/GSH ratio is a simple assay which could be validated as a novel clinical TM for the diagnosis and monitoring of CRC.This work was partially supported by grants GST, UGP-19-037 FISABIO, Universitat Politecnica de Valencia-the Hospital Universitario Doctor Peset POLISABIO collaboration program (UPV-FISABIO) NanOdGSens-2, the Spanish Government project RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE), the Generalitat Valenciana project PROMETEO/2018/024 and PI18/00932 by Instituto de Salud Carlos III and co-funded by the European Regional Development Fund (ERDF "A way to build Europe"). C.B. is a recipient of a Miguel Servet contract (CP19/00077) from the Instituto de Salud Carlos III.Acevedo-León, D.; Monzó-Beltrán, L.; Gómez-Abril, SÁ.; Estañ-Capel, N.; Camarasa-Lillo, N.; Pérez-Ebri, ML.; Escandón-Álvarez, J.... (2021). The Effectiveness of Glutathione Redox Status as a Possible Tumor Marker in Colorectal Cancer. International Journal of Molecular Sciences. 22(12):1-15. https://doi.org/10.3390/ijms22126183115221

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Un protocolo de embriogénesis somática para la regeneración y caracterización in vitro de Laelia Anceps Ssp. Dawsonii

Laelia anceps subespecie dawsonii, es una de las orquídeas silvestres mexicanas más apreciadas, con potencial ornamental por sus atractivas características que le permiten cumplir estándares internacionales de calidad y la convierten en una especie económicamente importante. Ello ha provocado su colecta excesiva y el consecuente riesgo de extinción. Para asegurar su conservación, es necesario desarrollar protocolos eficientes de propagación para esta especie, que permitan su uso sustentable y reduzcan la colecta. La embriogénesis somática constituye una tecnología eficiente para la multiplicación in vitro de especies vegetales. En este estudio, se evaluaron las condiciones in vitro para desarrollar un protocolo de embriogénesis somática para Laelia anceps ssp. dawsonii. A partir de semillas se indujo callo embriogénico en el medio Murashige y Skoog suplementado con ácido naftalénacético (ANA), 6-bencilami-nopurina (BAP), cinetina (Kin) y ácido indol acético (AIA), en combinaciones múltiples. La combinación ANA+BAP+AIA (2 mg L-1 de cada una) resultó óptima para inducción de callo pues produjo 611 embriones somáticos en fotoperiodo de 16 h (33.8 ¿mol m-2 s-1), con tres subcultivos a intervalos de 45 d en el mismo medio de cultivo, en el que además los embriones desarrollaron plántulas completas. En aproximadamente tres meses, las plántulas alcanzaron 4 a 5 cm en el medio Vacin y Went suplementado con BAP (2 mg L-1), AIA (1 mg L-1) y carbón activado (0.2 %), y después de 30 d, se aclimataron en invernadero, con 95 % de sobrevivencia

Mejor biblioteca, mejores lectores

El objetivo principal de este proyecto es poner en marcha una biblioteca escolar en el centro y como consecuencia directa, contribuir a la formación de nuevos y mejores lectores. Se necesita acondicionar un espacio acogedor y agradable, seleccionar un mobiliario práctico y conservarlo en buenas condiciones. En cuanto a los fondos, se debe facilitar el acceso y la rápida localización de los mismos, crear una sección de libros escritos por alumnos, aumentar la sección de libros en inglés, además de regular la adquisición y mantenimiento de los libros. Otro de los objetivos está relacionado con la gestión de la biblioteca como poner en funcionamiento el servicio de préstamo, elaborar un horario, un calendario, crear unas normas de uso y disfrute y preparar exposiciones, jornadas culturales, celebrar el día del Libro, editar un periódico, elaborar guías de lectura y actividades de animación a la lectura. Por tanto, las actividades se dividen en tres tipos: la relacionada con la transformación de la biblioteca, la relacionada con las actividades pedagógicas y la relacionada con la formación del profesorado. La metodología consiste en trabajar en equipo, a veces de forma voluntaria y otras programadas por los profesores. La evaluación del proyecto valora las actividades realizadas a lo largo del curso de forma continua, a través del diálogo con la coordinadora. Ésta se dedica a evaluar cada sesión o actividad mediante la observación directa y la redacción de informes con los resultados obtenidos. Adjunta anexos con números del periódico, folletos, fotografías y ejercicios..Madrid (Comunidad Autónoma). Consejería de Educación. Dirección General de Mejora de la Calidad de la EnseñanzaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort

CatedresBackground: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

WOS: 000481590200024PubMed ID: 31427717Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern.Spanish Ministry of Health (Instituto de Salud Carlos III/FEDER) [PI15/01159]; Crowdfunding program PRECIPITA, from the Spanish Ministry of Health (Fundacion Espanola para la Ciencia y la Tecnologia); Catalan Association for Rett Syndrome; Fondobiorett; Mi Princesa RettWe thank all patients and their families who contributed to this study. The work was supported by grants from the Spanish Ministry of Health (Instituto de Salud Carlos III/FEDER, PI15/01159); Crowdfunding program PRECIPITA, from the Spanish Ministry of Health (Fundacion Espanola para la Ciencia y la Tecnologia); the Catalan Association for Rett Syndrome; Fondobiorett and Mi Princesa Rett