A simple approximation for the evaluation of the photon isoeffective dose in Boron Neutron Capture Therapy based on dose-independent weighting factors

The current methodology for determining the biological effect of Boron Neutron Capture Therapy (BNCT) has recently been questioned, and a more accurate framework based in the photon isoeffective dose has been proposed. In this work we derive a first order approximation to this quantity than can be easily evaluated even from limited data, as is the current situation in the radiobiology of BNCT. This procedure removes the main drawbacks of the current method and it is based on new weighting factors that, as a difference with the previously used, are true constants (dose independent). In addition to this, we apply the formalism to allow the comparison to a fractionated conventional radiotherapy treatment, for which there is a lot of knowledge from clinical practice. As an application, the photon isoeffective dose of a BNCT treatment for a brain tumor is estimated. An excel sheet used for these calculations is also provided as supplementary material and can be used also with user-provided input data for the estimation of the photon isoeffective dose for comparison with conventional radiotherapy, both to single and fractionated treatments.Departamento de Física Atómica, Molecular y Nuclear, Universidad de Granada, Granada, Spain. Institut Laue-Langevin. Grenoble, Rhône-Alpes, France. Departamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada, Granada, Spai

Plan de cuidados para la prevención y tratamiento del alcoholismo en mujeres con depresión

Introducción: Los pacientes que sufren de patología dual (comorbilidad de una enfermedad mental y un trastorno por abuso de sustancias), presentan mayores riesgos y peor calidad de vida que los que presentan solamenteuna de las patologías.Varios estudios han demostrado que la comorbilidad de depresión y alcoholismo supone una elevada prevalencia y un aumento de la severidad de ambas patologías, lo que la convierte en un importante problema de salud.Las causas de la patología dual de depresión y alcoholismo son, los factores de riesgo que tienen en común, la angustia provocada por la sintomatología depresiva, que puede llevar a los enfermos a usar el alcohol como vía de escape y desarrollar alcoholismo, o que el consumo patológico de alcoholprovoque una depresión.Objetivo: Debido a la frecuencia con la que se presenta, en este trabajo mehe centrado en cómo prevenir y tratar el alcoholismo en mujeres con depresión, ya que en ellas la depresión suele ser la desencadenante del alcoholismo.Metodología: Para ello, he realizado una búsqueda bibliográfica para obtener información sobre estas patologías, y elaborar un plan de cuidados estandarizado. En él he analizado los problemas de salud, establecido objetivos y elaborado estrategias para mejorar la calidad de vida de los pacientes con esta comorbilidad o riesgo de ella.Conclusión: La falta de reconocimiento de la enfermedad y de adherencia terapéutica, son obstáculos que suelen presentar los pacientes alcohólicos y los que padecen depresión. Para resolverlos, es importante conocer los factores de riesgo y problemas de salud existentes en estos pacientes para detectar a las personas vulnerables y aplicarles la valoración diagnóstica y tratamiento que proceda. Es imprescindible crear una relación terapéutica positiva, entre el enfermo y el equipo sanitario multidisciplinar que le acompañará en su tratamiento, lo que fomentará una adecuada adherencia terapéutica.<br /

Neutron radiobiology studies with a pure cold neutron beam

Data on the radiobiological effects of thermal neutrons are usually obtained from irradiations in a mixed field of neutrons of different energies and gamma rays or from conversion of proton data with similar energies to those created in the neutron capture on nitrogen. Experimental data from irradiations in a pure thermal or cold neutron beam can help to find new values for neutron relative biological effectiveness (RBE) factors, which are useful for BNCT (Boron Neutron Capture Therapy) and radiation protection applications. We present a new experimental setup for radiobiological studies at a cold neutron beam at Institut Laue-Langevin, a beam without fast neutron component and almost no gamma ray contribution. After the irradiation, survival assays are performed to obtain the survival curves. Finally, comparing with a reference photon irradiation, the thermal neutron RBE factors can be calculated. The methodology is outlined at the example of A375 melanoma cells for which new radiobiological data were obtained.We acknowledge financial support for this work from the Fundación Científica de la Asociación Española Contra el Cáncer (AECC) under grant PS16163811PORR, Junta de Andalucía (Andalusian Regional Government), under contract P11-FQM-8229, Spanish MINECO and FEDER funds under contract FIS2015-69941-C2-1-P, the grant agreement ILL-UGR and the founders of the University of Granada Chair Neutrons for Medicine: Spanish Fundación ACS and Capitán Antonio. M.P. acknowledges a grant under the program Becas de Iniciación a la Investigación from the Universidad de Granada (Plan Propio de Investigación). The open access fee was covered by FILL2030, a European Union project within the European Commission’s Horizon 2020 Research and Innovation programme under grant agreement N°731096

Influence of the ectopic location on the antigen expression and functional characteristics of endometrioma stromal cells

Research question: Are the alterations observed in the endometriotic cells, such as progesterone resistance, already present in the eutopic endometrium or acquired in the ectopic location? Design: The response to decidualization with progesterone and cyclic AMP for up to 28 days was compared in different endometrial stromal cell (EnSC) lines established from samples of endometriomas (eEnSC), eutopic endometrium from women with endometriosis (eBEnSC), endometrial tissue from healthy women (BEnSC) and menstrual blood from healthy donors (mEnSC). Results: Usual features of decidualized cells, such as changes in cell morphology and expression of prolactin, were similarly observed in the three types of eutopic EnSC studied, but not in the ectopic cells upon decidualization. Among the phenotypic markers analysed, CD105 was down-regulated under decidualization in all cell types (mEnSC, P = 0.005; BEnSC, P = 0.029; eBEnSC, P = 0.022) except eEnSC. mEnSC and BEnSC underwent apoptosis during decidualization, whereas eBEnSC and eEnSC were resistant to the induction of cell death. Lastly, migration studies revealed that mEnSC secreted undetermined factors during decidualization that inhibited cell motility, whereas eEnSC showed a significantly lower ability to produce those migration-regulating factors (P < 0.0001, P  < 0.001 and P = 0.0013 for the migration of mEnSC at 24, 48 and 72 h, respectively; P  < 0.0001 for the migration of eEnSC at all times studied). Conclusions: This study provides novel insights into the differences between endometriotic and eutopic endometrial cells and reinforces the idea that the microenvironment in the ectopic location plays additional roles in the acquisition of the alterations that characterize the cells of the endometriotic foci.This work was supported by the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016, ISCIII Subdirección General de Evaluación y Fomento de la Investigación, Ministerio de Economía y Competitividad, Spain (Grant PI16/01642); the European Regional Development Fund (ERDF/634 FEDER funding); and the Plan Propio, Universidad de Granada (Grant PP2021.PP-12)

Menstrual blood‑derived stromal cells modulate functional properties of mouse and human macrophages

Menstrual blood-derived stromal cells (MenSCs) are emerging as a strong candidate for cell-based therapies due to their immunomodulatory properties. However, their direct impact on innate immune populations remains elusive. Since macrophages play a key role in the onset and development of inflammation, understanding MenSCs implication in the functional properties of these cells is required to refine their clinical effects during the treatment of inflammatory disorders. In this study, we assessed the effects that MenSCs had on the recruitment of macrophages and other innate immune cells in two mouse models of acute inflammation, a thioglycollate (TGC)-elicited peritonitis model and a monobacterial sepsis model. We found that, in the TGC model, MenSCs injection reduced the percentage of macrophages recruited to the peritoneum and promoted the generation of peritoneal immune cell aggregates. In the sepsis model, MenSCs exacerbated infection by diminishing the recruitment of macrophages and neutrophils to the site of infection and inducing defective bacterial clearance. Additional in vitro studies confirmed that co-culture with MenSCs impaired macrophage bactericidal properties, affecting bacterial killing and the production of reactive oxygen intermediates. Our findings suggest that MenSCs modulate the macrophage population and that this modulation must be taken into consideration when it comes to future clinical applications.Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016, ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, Ministerio de Economía y Competitividad, Spain PI16/01642 PI10/01096European Union (EU)Catedra de Investigación Antonio Chamorro-Alejandro Otero, Universidad de Granada CACH2017-

Decidualized human decidual stromal cells inhibit chemotaxis of activated T cells: a potential mechanism of maternal-fetal immune tolerance

Numerous lines of evidence confirm that decidual stromal cells (DSCs) play a key role in maternal–fetal immune tolerance. Under the influence of progesterone and other hormones, the DSCs go through a process of differentiation (decidualization) during normal pregnancy. In mice, DSCs inhibit the expression of chemokines that attract abortigenic Th1 and Tc cells to the decidua. We have studied this phenomenon in humans. Methods: We established human DSC lines and decidualized these cells in vitro with progesterone and cAMP. We determined the expression of the chemokines CXCL9, CXCL10 and CXCL11, whose receptor CXCR3 is expressed by Th1 and Tc cells, in undifferentiated DSCs and decidualized DSCs by qRT-PCR. Activated CD3+CXCR3+ cells, including CD4+ Th1 cells and CD8+ Tc cells, were induced in vitro. The migration capacity of these activated lymphocytes was investigated in Transwell chambers with conditioned media from undifferentiated and decidualized DSCs. Results: We demonstrated that CXCL9 was not expressed by DSCs, whereas the expression of CXCL10 and CXCL11 was inhibited in decidualized cells. Conditioned media from decidualized cells significantly inhibited the migration of Th1 and Tc cells.Wefound that decidualized cells secrete factors ofMWless than 6000–8000 Da, which actively inhibit the chemotaxis of these lymphocytes. Discussion: These results confirm in humans that decidualization of DSCs inhibits the expression by these cells of chemokines that attract Th1 and Tc cells and induces the secretion by DSCs of factors that inhibit the chemotaxis of these lymphocytes, thus preventing the arrival of abortigenic T cells in the decidua.Financial support was provided by Proyectos de I+D+I through the Programa Operativo Feder Andalucı́a (Grant B-CTS-228-UGR20

BNCT research activities at the Granada group and the project NeMeSis: Neutrons for medicine and sciences, towards an accelerator-based facility for new BNCT therapies, medical isotope production and other scientific neutron applications

The Granada group in BNCT research is currently performing studies on: nuclear and radiobiological data for BNCT, new boron compounds and a new design for a neutron source for BNCT and other applications, including the production of medical radioisotopes. All these activities are described in this report.Asociación Española Contra el Cáncer (AECC) PS16163811PORRSpanish MINECO FIS2015-69941-C2-1-PJunta de Andalucía P11-FQM-8229Campus of International Excellence BioTic P-BS-64Spanish Fundacion ACSAsociación Capitán AntonioLa Kuadrilla de IznallozSonriendo se Puede Gana

SLAMF8 Downregulates Mouse Macrophage Microbicidal Mechanisms via PI3K Pathways

SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2022.910112/ full#supplementary-materialACKNOWLEDGMENTS SR-P is a PhD student belonging to the Official Doctoral Program in Biomedicine of the University of Granada. The authors thank Dr. Ana Santos Carro and Dr. David Porcell from the Center of Technical Instrumentation, University of Granada, for their excellent technical assistance with confocal microscopy, and Dr. M.C. Ruiz-Ruiz and Dr. Silvia Calpe-Flores for revising the manuscript.Signaling lymphocytic activation molecule family 8 (SLAMF8) is involved in the negative modulation of NADPH oxidase activation. However, the impact of SLAMF8 downregulation on macrophage functionality and the microbicide mechanism remains elusive. To study this in depth, we first analyzed NADPH oxidase activation pathways in wild-type and SLAMF8-deficient macrophages upon different stimulus. Herein, we describe increased phosphorylation of the Erk1/2 and p38 MAP kinases, as well as increased phosphorylation of NADPH oxidase subunits in SLAMF8-deficient macrophages. Furthermore, using specific inhibitors, we observed that specific PI3K inhibition decreased the differences observed between wild-type and SLAMF8-deficient macrophages, stimulated with either PMA, LPS, or Salmonella typhimurium infection. Consequently, SLAMF8-deficient macrophages also showed increased recruitment of small GTPases such as Rab5 and Rab7, and the p47phox subunit to cytoplasmic Salmonella, suggesting an impairment of Salmonella-containing vacuole (SCV) progression in SLAMF8-deficient macrophages. Enhanced iNOS activation, NO production, and IL-6 expression were also observed in the absence of SLAMF8 upon Salmonella infection, either in vivo or in vitro, while overexpression of SLAMF8 in RAW264.7 macrophages showed the opposite phenotype. In addition, SLAMF8-deficient macrophages showed increased activation of Src kinases and reduced SHP-1 phosphate levels upon IFNγ and Salmonella stimuli in comparison to wild-type macrophages. In agreement with in vitro results, Salmonella clearance was augmented in SLAMF8-deficient mice compared to that in wild-type mice. Therefore, in conclusion, SLAMF8 intervention upon bacterial infection downregulates mouse macrophage activation, and confirmed that SLAMF8 receptor could be a potential therapeutic target for the treatment of severe or unresolved inflammatory conditions.Plan Estatal de Investigación Científica y Ténica y de Innovación, ISCIII Subdirección General de Evaluación y Fomento de la Investigación, Ministerio de Economía y Competitividad, Spain (Grants PI16/01642 and PI10/01096

Primer consenso en leucemia linfocítica crónica de la agrupación mexicana para el estudio de la hematología: epidemiología, diagnóstico y tratamiento

La leucemia linfocítica crónica (LLC) es la leucemia crónica menos frecuente en México. En consideración a los avances recientes, a una mejor clasificación pronóstica y a la introducción de nuevas modalidades terapéuticas, la Agrupación Mexicana para el Estudio de la Hematología organizó el primer consenso mexicano en leucemia linfocítica crónica. Este consenso se llevó a cabo en Cancún, Quintana Roo, México, en Septiembre del 2007. Los objetivos de esta reunión fueron actualizar y compartir los conocimientos de la enfermedad entre los especialistas mexicanos, con el fin de mejorar el diagnóstico y el pronóstico de la LLC en México. En el artículo se discute los aspectos clínicos, diagnósticos y terapéuticos de la LLC