SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis.

SETD8 is a methyltransferase that is overexpressed in several cancers, which monomethylates H4K20 as well as other non-histone targets such as PCNA or p53. We here report novel SETD8 inhibitors, which were discovered while trying to identify chemicals that prevent 53BP1 foci formation, an event mediated by H4K20 methylation. Consistent with previous reports, SETD8 inhibitors induce p53 expression, although they are equally toxic for p53 proficient or deficient cells.

Gastrointestinal symptoms and nutritional intake among participants in a non-professional cycling event.

Purpose: To determine the occurrence of gastrointestinal (GI) symptoms in different settings among cyclists participating in a non-professional cycling event. The nutritional intake during the event and the association between GI symptoms and both nutritional and non-nutritional factors were also analyzed.

Methods: A descriptive correlational study was performed among participants in the 2023 'Mallorca 312-Milestone Series' cycling event.

Machine learning identifies experimental brain metastasis subtypes based on their influence on neural circuits.

A high percentage of patients with brain metastases frequently develop neurocognitive symptoms; however, understanding how brain metastasis co-opts the function of neuronal circuits beyond a tumor mass effect remains unknown. We report a comprehensive multidimensional modeling of brain functional analyses in the context of brain metastasis. By testing different preclinical models of brain metastasis from various primary sources and oncogenic profiles, we dissociated the heterogeneous impact on local field potential oscillatory activity from cortical and hippocampal areas that we detected from the homogeneous inter-model tumor size or glial response.

Phylogenetic study and comparison of different TbpB obtained from Glaesserella parasuis present in Spanish clinical isolates.

Glaesserella parasuis (Gp) is the etiological agent of Glässer's disease (GD), which causes important economic losses for the pig intensive production worldwide. This organism uses a smart protein-based receptor to acquire specifically iron from the porcine transferrin. This surface receptor consists of transferrin-binding protein A (TbpA) and transferrin-binding protein B (TbpB).

Caffeine Intake among Undergraduate Students: Sex Differences, Sources, Motivations, and Associations with Smoking Status and Self-Reported Sleep Quality.

Due to its stimulatory effects, caffeine is one of the most frequently consumed mood and behavior altering drugs. University students report using caffeine-containing products to enhance mood and performance or for a desire of alertness. The current study investigated caffeine consumption in university undergraduate students, and associations with smoking status, alcohol and cannabis consumption, fruit and vegetable consumption, and sleep quality.

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.

We report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery.

Blood Cell In Vitro Cytokine Production in Response to Lipopolysaccharide Stimulation in a Healthy Population: Effects of Age, Sex, and Smoking.

Immune system functionality has been commonly assessed by a whole-blood or isolated-cell stimulation assay. The aim of this study was to determine whether cytokine production in whole-blood-stimulated samples is influenced by age, sex, and smoking. A descriptive cross-sectional study in 253 healthy participants aged 18-55 years was conducted.

The Role of the pH in the Impregnation of Spherical Mesoporous Silica Particles with L-Arginine Aqueous Solutions.

In the context of the development of carriers for amino acids delivery, Spherical Mesoporous Silica Particles (SMSP), characterized by particles size ranging from 0.15 µm to 0.80 µm and average pore diameter of 2.

[Clinical guidelines for the managment of intestinal failure secondary to pediatric short bowel syndrome].

Intestinal failure secondary to short bowel syndrome in pediatrics, is a rare condition with high morbimortality. A follow up multidisciplinary team is necessary to minimize complications and optimize the intestinal rehabilitation. There are no gold standard guidelines for the management of this group of complex patients.

Nutritional Status and Implementation of a Nutritional Education Program in Young Female Artistic Gymnasts.

Adolescent high-performance gymnasts are considered to be at risk for low energy intake. The aim of the present study was to determine the effects of implementing a nutritional education program during the sports season on the nutritional status and nutrition knowledge of the female artistic gymnasts from the Technification Center of the Balearic Islands (n = 24; age, 14.1 ± 2.

Executive Function Training in Childhood Obesity: Food Choice, Quality of Life, and Brain Connectivity (TOuCH): A Randomized Control Trial Protocol.

Individuals with obesity are known to present cognitive deficits, especially in executive functions. Executive functions play an important role in health and success throughout the whole life and have been related to food decision-making and to the ability to maintain energy balance. It is possible to improve executive functions through targeted training.

Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases.

Pluripotent stem cells (PSCs) transition between cell states in vitro, reflecting developmental changes in the early embryo. PSCs can be stabilized in the naive state by blocking extracellular differentiation stimuli, particularly FGF-MEK signalling. Here, we report that multiple features of the naive state in human and mouse PSCs can be recapitulated without affecting FGF-MEK signalling or global DNA methylation.

Caffeine supplementation induces higher IL-6 and IL-10 plasma levels in response to a treadmill exercise test.

Background: An acute bout of exercise induces an inflammatory response characterized by increases in several cytokines. Caffeine ingestion could modify this inflammatory response. The aim of this study was to determine the effects of caffeine supplementation on plasma levels of cytokines, mainly IL-10 and IL-6, in response to exercise.

Effects of Habitual Caffeine Intake, Physical Activity Levels, and Sedentary Behavior on the Inflammatory Status in a Healthy Population.

Low-grade chronic inflammation is associated with many chronic diseases and pathological conditions. The aim of the present study was to determine the effect of regular caffeine intake, physical activity levels, and sedentary behavior on the inflammatory status in healthy participants. In total, 112 men and 132 women aged 18 to 55 years and belonging to the staff and student population of the University of the Balearic Islands volunteered to participate in this descriptive cross-sectional study.

Antimicrobial Susceptibility Pattern of Porcine Respiratory Bacteria in Spain.

The monitoring of antimicrobial susceptibility of pig pathogens is critical to optimize antimicrobial treatments and prevent development of resistance with a one-health approach. The aim of this study was to investigate the antimicrobial susceptibility patterns of swine respiratory pathogens in Spain from 2017 to 2019. Bacterial isolation and identification were carried out following standardized methods from samples coming from sacrificed or recently deceased pigs with acute clinical signs compatible with respiratory tract infections.

How consistent is RAD-seq divergence with DNA-barcode based clustering in insects?

Promoted by the barcoding approach, mitochondrial DNA is more than ever used as a molecular marker to identify species boundaries. Yet, it has been repeatedly argued that it may be poorly suited for this purpose, especially in insects where mitochondria are often associated with invasive intracellular bacteria that may promote their introgression. Here, we inform this debate by assessing how divergent nuclear genomes can be when mitochondrial barcodes indicate very high proximity.

Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer.

The proviral integration of Moloney virus (PIM) family of protein kinases are overexpressed in many haematological and solid tumours. PIM kinase expression is elevated in PI3K inhibitor-treated breast cancer samples, suggesting a major resistance pathway for PI3K inhibitors in breast cancer, potentially limiting their clinical utility. IBL-302 is a novel molecule that inhibits both PIM and PI3K/AKT/mTOR signalling.

The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status.

Resistance to anaplastic lymphoma kinase (ALK)-targeted therapy in ALK-positive non-small cell lung cancer has been reported, with the majority of acquired resistance mechanisms relying on bypass signaling. To proactively identify resistance mechanisms in ALK-positive neuroblastoma (NB), we herein employ genome-wide CRISPR activation screens of NB cell lines treated with brigatinib or ceritinib, identifying PIM1 as a putative resistance gene, whose high expression is associated with high-risk disease and poor survival. Knockdown of PIM1 sensitizes cells of differing MYCN status to ALK inhibitors, and in patient-derived xenografts of high-risk NB harboring ALK mutations, the combination of the ALK inhibitor ceritinib and PIM1 inhibitor AZD1208 shows significantly enhanced anti-tumor efficacy relative to single agents.

Acute acetaminophen intoxication induces direct neurotoxicity in rats manifested as astrogliosis and decreased dopaminergic markers in brain areas associated with locomotor regulation.

Acetaminophen (APAP) administration at therapeutic doses is safe, however overdosing produces hepatocellular injury via a multifactorial mechanism(s) that involves generation of reactive oxygen species (ROS), being the most common cause of acute liver failure (ALF) in the northern hemisphere. Brain alterations induced by APAP intoxication are usually considered secondary to hepatic encephalopathy development due to ALF. Although APAP is primarily metabolized in the liver, it is also distributed and metabolized homogeneously in the brain, affecting brain redox status.

Identifying the relationship between biological, psychosocial and family markers associated with childhood obesity: Case-control "ANOBAS" study.

The recent increase in childhood obesity prevalence rates illustrates the extreme relevance of biological, psychosocial and familial factors implicated in body weight status, which at the moment remain unclear. The study aims to compare biological, psychosocial and familial markers between preadolescents with obesity and their non-overweight peers, and explore the relationship with psychiatric diagnosis on these markers. Both groups were composed of 40% of males with a mean age of 10 years, and no differences in socio-demographic variables were found between groups.

Screening protocol for the identification of modulators by immunofluorescent cell-based assay.

High-throughput assays are a common strategy for the identification of compounds able to modulate a certain cellular activity. Here, we show an automatized analysis platform for the quantification of nuclear foci as inhibitory effect of compounds on a target protein labeled by fluorescent antibodies. Our experience led us to a fast analysis platform that combines cell-based assays, high-content screening, and confocal microscopy, with an automatic and user-friendly statistical analysis of plate-based assays including positive and negative controls, able to identify inhibitory effect of compounds tested together with the Z-prime and Window of individual plate-based assays to assess the reliability of the results.

Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma.

The PI3K pathway is a major driver of cancer progression. However, clinical resistance to PI3K inhibition is common. IBL-302 is a novel highly specific triple PIM, PI3K, and mTOR inhibitor.