Contribution of C3G and other GEFs to liver cancer development and progression

Primary liver cancers constitute the fourth leading cause of cancer mortality worldwide, due to their high morbidity, late diagnosis and lack of effective treat...     

Exposiciones laborales,dieta y envasado: recomendaciones para reducir los contaminantes medioambientales en la lactancia materna

The pollution of the planet also reaches the breastfeeding ecosystem, one of the most intimate and inviolable that links us as an animal species to the rest of mammals. Nursing mothers may be concerned about whether the quality of their milk will be adequate for their baby and whether environmental pollutants through work, diet, and storing may adversely affect their child. Breast milk is a source of exposure to environmental pollutants, and at the same time it counteracts much of the effects of these exposures. An approach based on the principles of reality and precaution of environmental health to avoid, reduce or eliminate the production and use of harmful chemicals during pregnancy and lactation would improve the human and planetary health for the offspring.     

The Polycomb group protein RING1B is overexpressed in ductal breast carcinoma and is required to sustain FAK steady state levels in breast cancer epithelial cells

In early stages of metastasis malignant cells must acquire phenotypic changes to enhance their migratory behavior and their ability to breach the matrix surrounding tumors and blood vessel walls. Epigenetic regulation of gene expression allows the acquisition of these features that, once tumoral cells have escape from the primary tumor, can be reverted. Here we report that the expression of the Polycomb epigenetic repressor Ring1B is enhanced in tumoral cells that invade the stroma in human ductal breast carcinoma and its expression is coincident with that of Fak in these tumors. Ring1B knockdown in breast cancer cell lines revealed that Ring1B is required to sustain Fak expression in basal conditions as well as in Tgfβ-treated cells. Functionally, endogenous Ring1B is required for cell migration and invasion in vitro and for in vivo invasion of the mammary fat pad by tumoral cells. Finally we identify p63 as a target of Ring1B to regulate Fak expression: Ring1B depletion results in enhanced p63 expression, which in turns represses Fak expression. Importantly, Fak downregulation upon Ring1B depletion is dependent on p63 expression. Our findings provide new insights in the biology of the breast carcinoma and open new avenues for breast cancer prognosis and therapy.     

Treatment preferences as basis for decision making in patients using direct oral anticoagulants in Spain

Journal of Thrombosis and Thrombolysis - Treatment preferences are considered a relevant decision-making driver by the main atrial fibrillation (AF) guidelines. Direct Oral Anticoagulants (DOACs),...     

Effectiveness of interventions aimed at improving grief and depression in caregivers of people with dementia: A systematic review and meta-analysis

Caregivers of people suffering from dementia may go through a grieving process prior to the death of the cared-for person, which is related to mental health and physical problems. Interventions aimed at improving grief and depression are being used in response to these difficulties. The aim of this study was to synthesize and evaluate the evidence for the effectiveness of interventions aimed at improving the grief process in home-based caregivers of people with dementia with the aim of reducing grief and depression. A systematic review, including a meta-analysis, was designed. Following the PRISMA guideline, original articles were searched in the databases: Medline, WOS, Scopus and PsycINFO, up to September 2022. Articles that evaluated interventions aimed at improving the grief process in caregivers of people with dementia, whose care recipients were alive at the beginning of the study at minimum and living at home were selected. Grief and depression were considered outcome variables. A meta-analysis was carried out with a fixed effects model for these variables and for the domains of the Caregiver Grief Scale (CGS). Eight articles met the inclusion and exclusion criteria. Most of the interventions aimed at improving the grief process showed an improvement in grief and depression. The ‘emotional pain’ and ‘absolute loss’ domains of the CGS stood out with an improvement in these variables. Interventions aimed at improving the grief process are relatively effective in reducing grief and depression. Interventions that are even more effective and more robust studies are needed.     

Upadacitinib effectiveness in moderate-to-severe atopic dermatitis: A real-life multicentre and retrospective study

This was an observational and retrospective multicentre study conducted on adolescents and adults diagnosed with moderate-to-severe atopic dermatitis (AD) and treated with upadacitinib. Disease severity was measured by Eczema Area and Severity Index (EASI), validated investigator global assessment for AD and pruritus Numerical Rating Scale (NRS) at baseline and Weeks 4, 16, 24 and 52 (when available). Twenty-one patients were included. All patients had previously received topical and systemic corticosteroids. Rapid response to upadacitinib was observed: Mean (SD) EASI score was 19.8 (6.5) at baseline, and 3.1 (4.2), 0.9 (1.4), 0.6 (0.6) and 0.6 (0.6) at the Weeks 4, 16, 24 and 52, respectively. Itch was controlled at Week 4 in all patients (mean [SD] NRS score 7.6 [1.9] baseline, 1.5 [1.3] W4). Severe infections or major adverse cardiovascular events were not reported. We highlight effectiveness and rapid response of upadacitinib in achieving itch control even in long-standing recalcitrant cases.     

Increased let-7d-5p in non-alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis

Background and Aims

The molecular mechanisms driving non-alcoholic fatty liver disease (NAFLD) are poorly understood; however, microRNAs might play a key role in these processes. We hypothesize that let-7d-5p could contribute to the pathophysiology of NAFLD and serve as a potential diagnostic biomarker.

Methods

We evaluated let-7d-5p levels and its targets in liver biopsies from a cross-sectional study including patients with NAFLD and healthy donors, and from a mouse model of NAFLD. Moreover, the induction of let-7d-5p expression by fatty acids was evaluated in vitro. Further, we overexpressed let-7d-5p in vitro to corroborate the results observed in vivo. Circulating let-7d-5p and its potential as a NAFLD biomarker was determined in isolated extracellular vesicles from human plasma by RT-qPCR.

Results

Our results demonstrate that hepatic let-7d-5p was significantly up-regulated in patients with steatosis, and this increase correlated with obesity and a decreased expression of AKT serine/threonine kinase (AKT), insulin-like growth factor 1 (IGF1), IGF-I receptor (IGF1R) and insulin receptor (INSR). These alterations were corroborated in a NAFLD mouse model. In vitro, fatty acids increased let-7d-5p expression, and its overexpression decreased AKT, IGF-IR and IR protein expression. Furthermore, let-7d-5p hindered AKT phosphorylation in vitro after insulin stimulation. Finally, circulating let-7d-5p significantly decreased in steatosis patients and receiver operating characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker.

Conclusions

Our results highlight the emerging role of let-7d-5p as a potential therapeutic target for NAFLD since its overexpression impairs hepatic insulin signalling, and also, as a novel non-invasive biomarker for NAFLD diagnosis.     

Effects of exercise timing on metabolic health

The increasing prevalence of metabolic syndrome is associated with major health and socioeconomic consequences. Currently, physical exercise, together with dietary interventions, is the mainstay of the treatment of obesity and related metabolic complications. Although exercise training includes different modalities, with variable intensity, duration, volume, or frequency, which may have a distinct impact on several characteristics related to metabolic syndrome, the potential effects of exercise timing on metabolic health are yet to be fully elucidated. Remarkably, promising results with regard to this topic have been reported in the last few years. Similar to other time-based interventions, including nutritional therapy or drug administration, time-of-day-based exercise may become a useful approach for the management of metabolic disorders. In this article, we review the role of exercise timing in metabolic health and discuss the potential mechanisms that could drive the metabolic-related benefits of physical exercise performed in a time-dependent manner.     

Stressors and uplifts of confinement due to covid-19: A longitudinal study on mental health in a sample of academic and administrative university staff in Spain

The rapid spread of COVID-19 caused many countries to decide to enter full lockdown, a circumstance that impacted all aspects of life, including mental health. The present longitudinal study aimed to analyse how stressors and uplifts of confinement were linked to psychological symptoms at three different time points: during the full lockdown (wave 1), after the gradual lifting of restrictions (wave 2) and after confinement (wave 3). The sample was made up by one hundred and twenty academic and administrative staff from a big University in Spain, they all completed an online survey. Results showed that psychological status did not change over time, but a significant interindividual variability was found throughout. Some stressors were only linked to symptoms at wave 1, but others maintained their associations during waves 2 and 3. Uplifts were, for the most part, inversely (and exclusively) linked to symptoms at wave 1. However, some of them, although enjoyable, were paradoxically linked to worse mental health at wave 1, and even at waves 2 and 3. These findings highlight the importance of providing preventive psychological strategies for mental distress before, during and after confinement.