c-Src functionality controls self-renewal and glucose metabolism in MCF7 breast cancer stem cells

Deregulation of Src kinases is associated with cancer. We previously showed that SrcDN conditional expression in MCF7 cells reduces tumorigenesis and causes tumor regression in mice. However, it remained unclear whether SrcDN affected breast cancer stem cell functionality or it reduced tumor mass. Here, we address this question by isolating an enriched population of Breast Cancer Stem Cells (BCSCs) from MCF7 cells with inducible expression of SrcDN. Induction of SrcDN inhibited self-renewal, and stem-cell marker expression (Nanog, Oct3-4, ALDH1, CD44). Quantitative proteomic analyses of mammospheres from MCF7-Tet-On-SrcDN cells (data are available via ProteomeXchange with identifier PXD017789, project DOI: 10.6019/PXD017789) and subsequent GSEA showed that SrcDN expression inhibited glycolysis. Indeed, induction of SrcDN inhibited expression and activity of hexokinase, pyruvate kinase and lactate dehydrogenase, resulting in diminished glucose consumption and lactate production, which restricted Warburg effect. Thus, c-Src functionality is important for breast cancer stem cell maintenance and renewal, and stem cell transcription factor expression, effects linked to glucose metabolism reduction.This work has been supported by grand SAF2016–75991-R (MINECO, AEI/FEDER, UE) to Jorge Martín-Pérez and ISCIII [grand PI 16/00789] to Miguel Ángel Fernández-Moreno. Víctor Mayoral-Varo was supported by the grand SAF2016–75991-R (MINECO, AEI/FEDER, UE). We acknowledge support for publication fee by the CSIC Open Access Publication Support Initiative through its Unit for Information Resources for Research (URICI)

Funcionamiento familiar en adolescentes en riesgo de suicidio con rasgos de personalidad límite: un estudio exploratorio

La alta prevalencia de suicidio en población adolescente en todo el mundo supone un reto mundial en salud mental. El ambiente familiar ha sido señalado como una importante variable implicada en el riesgo de suicidio de los adolescentes, ejerciendo tanto de factor de riesgo como protector. El estudio tiene como objetivo entender qué variables del funcionamiento familiar de la Escala de Clima Social en la Familia se relacionan con la puntuación de la Escala de Ideación Suicida de Beck en una muestra 37 adolescentes entre 14 y 18 años (M = 15.76; DT = 1.07) con rasgos de personalidad límite. Se partió de la hipótesis de que peores niveles de funcionamiento familiar aumentarían el riesgo de suicidio. Los resultados mostraron que la ideación suicida era mayor cuando las puntuaciones en la escala Relaciones (calidad de la comunicación e interacción) en la familia eran menores. Al analizar cada escala, se demostró la importancia específica de la subescala Expresividad, referida al grado de expresión libre de los sentimientos en la familia de forma que, a menor expresividad en la familia, mayor ideación suicida presentaban los adolescentes, y la subescala Social-Recreativa, referida a la participación social y en actividades de ocio de la familia, de modo que a mayor participación social, menor riesgo suicida. Estos resultados son apoyados por otros estudios que demuestran la importancia de modificar el entorno familiar para influir en el riesgo suicida de los adolescentes. El valor de estos datos implica la consideración de incluir a las familias en los programas de tratamiento para adolescentes suicidas.Family functioning in suicidal adolescents with borderline personality traits. High prevalence of suicide in adolescent population all over the world is considered a world challenge in mental health. Family environment has been pointed as an important factor involved in adolescents’ suicide risk, playing a role not only as a risk factor but also as protective. This study has its goal on understanding which factors of the family functioning, measured by the Social Environment in the Family Scale, are related to the total score of the Beck Suicide Ideation Scale in a sample of 37 adolescents with ages between 14 and 17 years old (M = 15.76; SD = 1.06) borderline personality traits. It was hypothesized that worse levels of family functioning will increase suicide risk in adolescents. Results showed that the risk of suicide was higher when the Relationships Scale total score (quality of communication and interaction in the family) was lower. After analyzing each subscale separately, it was demonstrated the specific relevance of Expressivity Subscale, referred to the level of free expression of feelings in the family, suggesting that the lower expressivity in the family, the higher suicide ideation showed by the adolescents, and Social-Recreative, referred to the social participation and leisure of the family, what means the more social participation, the less suicide ideation. These results are supported by other studies that show the relevance of modifying the family environment for reducing the suicidal risk among adolescents. The value of this data involves taking into account the families in the treatment programs for suicidal adolescents

Antipsychotic Medication Influences the Discriminative Value of Acylethanolamides as Biomarkers of Substance Use Disorder.

Plasma acylethanolamides (NAEs), including the endocannabinoid anandamide (AEA), have been proposed as circulating biomarkers of substance use disorders. However, the concentration of these lipid transmitters might be influenced by the use of drugs prescribed for either the treatment of addiction or the associated psychiatric co-morbidities such as psychosis. As an example, neuroleptics, used for attenuation of psychotic symptoms and sedation, might theoretically interfere with the monoamine-mediated production of NAEs, obstructing the interpretation of plasma NAEs as clinical biomarkers. To solve the lack of information on the impact of neuroleptics on the concentration of NAEs, we evaluated the concentrations of NAEs in a control group and compared them to those present in (a) substance use disorders (SUD) patients that are not prescribed with neuroleptics, and (b) SUD patients (both alcohol use disorder and cocaine use disorder patients) using neuroleptics. The results demonstrate that SUD patients exhibited greater concentrations of NAEs than the control population, affecting all species with the exception of stearoylethanolamide (SEA) and palmitoleoylethanolamide (POEA). Neuroleptic treatment enhanced the concentrations of NAEs, especially those of AEA, linoleoylethanolamide (LEA), and oleoylethanolamide (OEA). This effect of neuroleptic treatment was observed independently of the drug addiction that motivated the demand for treatment (either alcohol or cocaine). This study remarks the need to control the current use of psychotropic medication as a potential confounding variable when considering the use of NAEs as biomarkers in SUDPartial funding for open access charge: Universidad de Málag

Estudio longitudinal del rendimiento neuropsicológico en psicosis de inicio en la infancia y la adolescencia

La investigación en psicosis de inicio temprano ha experimentado durante los últimos años un notable desarrollo. Las líneas de investigación en esta población están orientadas en gran medida a replicar datos que se han obtenido en población adulta. Esto se debe a que en la actualidad, uno de los aspectos a debate es la posibilidad de que la esquizofrenia de inicio temprano y la de inicio en la edad adulta constituyan la misma entidad clínica. En los últimos años se ha experimentado un interés científico creciente por los estudios longitudinales de primeros episodios psicóticos. Estos estudios se consideran necesarios para evaluar los cambios clínicos, funcionales, biológicos, así como las distintas interacciones entre ellos, a lo largo de los primeros años de la enfermedad. La inmensa mayoría de estos estudios se han realizado con pacientes que presentan un primer episodio psicótico a lo largo de la vida adulta, existiendo muy pocos estudios que hayan seguido longitudinalmente primeros episodios psicóticos en niños y adolescentes. En el caso de nuestro estudio, el diseño longitudinal nos permitirá valorar si existe un deterioro neuropsicológico a lo largo del tiempo como propone la hipótesis de neurodegeneración, comparando los resultados obtenidos en nuestro grupo de pacientes con la evolución de los controles sanos, cuyos datos supondrán también un interesante acercamiento a la comprensión del desarrollo del cerebro adolescente en sujetos sin patología

Funcionamiento familiar en adolescentes en riesgo de suicidio con rasgos de personalidad límite:: un estudio exploratorio

Family functioning in suicidal adolescents with borderline personality traits. High prevalence of suicide in adolescent population all over the world is considered a world challenge in mental health. Family environment has been pointed as an important factor involved in adolescents’ suicide risk, playing a role not only as a risk factor but also as protective. This study has its goal on understanding which factors of the family functioning, measured by the Social Environment in the Family Scale, are related to the total score of the Beck Suicide Ideation Scale in a sample of 37 adolescents with ages between 14 and 17 years old (M = 15.76; SD = 1.06) borderline personality traits. It was hypothesized that worse levels of family functioning will increase suicide risk in adolescents. Results showed that the risk of suicide was higher when the Relationships Scale total score (quality of communication and interaction in the family) was lower. After analyzing each subscale separately, it was demonstrated the specific relevance of Expressivity Subscale, referred to the level of free expression of feelings in the family, suggesting that the lower expressivity in the family, the higher suicide ideation showed by the adolescents, and Social-Recreative, referred to the social participation and leisure of the family, what means the more social participation, the less suicide ideation. These results are supported by other studies that show the relevance of modifying the family environment for reducing the suicidal risk among adolescents. The value of this data involves taking into account the families in the treatment programs for suicidal adolescentsLa alta prevalencia de suicidio en población adolescente en todo el mundo supone un reto mundial en salud mental. El ambiente familiar ha sido señalado como una importante variable implicada en el riesgo de suicidio de los adolescentes, ejerciendo tanto de factor de riesgo como protector. El estudio tiene como objetivo entender qué variables del funcionamiento familiar de la Escala de Clima Social en la Familia se relacionan con la puntuación de la Escala de Ideación Suicida de Beck en una muestra 37 adolescentes entre 14 y 18 años (M = 15.76; DT = 1.07) con rasgos de personalidad límite. Se partió de la hipótesis de que peores niveles de funcionamiento familiar aumentarían el riesgo de suicidio. Los resultados mostraron que la ideación suicida era mayor cuando las puntuaciones en la escala Relaciones (calidad de la comunicación e interacción) en la familia eran menores. Al analizar cada escala, se demostró la importancia específica de la subescala Expresividad, referida al grado de expresión libre de los sentimientos en la familia de forma que, a menor expresividad en la familia, mayor ideación suicida presentaban los adolescentes, y la subescala Social-Recreativa, referida a la participación social y en actividades de ocio de la familia, de modo que a mayor participación social, menor riesgo suicida. Estos resultados son apoyados por otros estudios que demuestran la importancia de modificar el entorno familiar para influir en el riesgo suicida de los adolescentes. El valor de estos datos implica la consideración de incluir a las familias en los programas de tratamiento para adolescentes suicidas

The Inflammatory Signals Associated with Psychosis: Impact of Comorbid Drug Abuse

Psychosis and substance use disorders are two diagnostic categories whose association has been studied for decades. In addition, both psychosis spectrum disorders and drug abuse have recently been linked to multiple pro-inflammatory changes in the central nervous system. We have carried out a narrative review of the literature through a holistic approach. We used PubMed as our search engine. We included in the review all relevant studies looking at pro-inflammatory changes in psychotic disorders and substance use disorders. We found that there are multiple studies that relate various pro-inflammatory lipids and proteins with psychosis and substance use disorders, with an overlap between the two. The main findings involve inflammatory mediators such as cytokines, chemokines, endocannabinoids, eicosanoids, lysophospholipds and/or bacterial products. Many of these findings are present in different phases of psychosis and in substance use disorders such as cannabis, cocaine, methamphetamines, alcohol and nicotine. Psychosis and substance use disorders may have a common origin in an abnormal neurodevelopment caused, among other factors, by a neuroinflammatory process. A possible convergent pathway is that which interrelates the transcriptional factors NFκB and PPARγ. This may have future clinical implications

The Inflammatory Signals Associated with Psychosis: Impact of Comorbid Drug Abuse

Psychosis and substance use disorders are two diagnostic categories whose association has been studied for decades. In addition, both psychosis spectrum disorders and drug abuse have recently been linked to multiple pro-inflammatory changes in the central nervous system. We have carried out a narrative review of the literature through a holistic approach. We used PubMed as our search engine. We included in the review all relevant studies looking at pro-inflammatory changes in psychotic disorders and substance use disorders. We found that there are multiple studies that relate various pro-inflammatory lipids and proteins with psychosis and substance use disorders, with an overlap between the two. The main findings involve inflammatory mediators such as cytokines, chemokines, endocannabinoids, eicosanoids, lysophospholipds and/or bacterial products. Many of these findings are present in different phases of psychosis and in substance use disorders such as cannabis, cocaine, methamphetamines, alcohol and nicotine. Psychosis and substance use disorders may have a common origin in an abnormal neurodevelopment caused, among other factors, by a neuroinflammatory process. A possible convergent pathway is that which interrelates the transcriptional factors NFκB and PPARγ. This may have future clinical implications

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols