Exosomes in head and neck cancer. Updating and revisiting

Exosomes have gone from being considered simple containers of intracellular waste substances to be considered important carriers of cellular signals. Its broad capacity to promote tumour growth, both in situ and metastatic, has greatly intensified scientific research on them. In the same way and depending on its content, its tumour suppressive properties have opened a window of light and hope in the fight against cancer. In the present review we try to gather in a simple and understandable way the most relevant knowledge to date on the role of exosomes in oral squamous cell carcinoma, helping to understand their process of formation, release and activity on the tumour microenvironment

Clinicopathological features of 214 maxillary sinus pathologies. A ten-year single-centre retrospective clinical study

BACKGROUND: Diagnosis of maxillary sinus pathology must include the clinical radiological study (CRS) and histopathological analysis. The aim of this study is 1) to describe the clinicopathological features of maxillary sinus lesions, obtained successively in a single medical centre over the last 10 years and 2) to determine the sensitivity and specificity for the diagnosis of malignant lesions based exclusively on the CRS. METHODS: It is a single-centre observational retrospective clinical study on patients who attended the University Hospital Complex of Santiago de Compostela (CHUS) with sinus pathologies during the period of 2009-2019. RESULTS: The sample consisted of 133 men (62.1%) and 81 women (37.9%), with an average age of 46.9 years (SD = 18.8). In terms of frequency, the most frequent pathology was the unspecified sinusitis (44.4%), followed by polyps (18.2%), malignant tumours (9.8%), inverting papilloma (7.5%), fungal sinusitis (4.7%), cysts (3.7%), benign tumours (2.3%), mucocele (2.3%) and other lesions (1.9%). Cysts and benign tumours were diagnosed earliest Vs malignant tumours (65.2 years (SD = 16.1)) were diagnosed the latest (p < 0.001). Based only on the CRS for malignancies, diagnostic indexes were 71.4% sensitivity and 97.9% specificity, with a Kappa value of 0.68 with (p < 0.001). CONCLUSION: Maxillary sinus pathology is very varied with therapeutic and prognostic repercussions. CRS is sometimes insufficient and histopathological confirmation is essential

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Astroglial Inhibition of NF-κB Does Not Ameliorate Disease Onset and Progression in a Mouse Model for Amyotrophic Lateral Sclerosis (ALS)

Motor neuron death in amyotrophic lateral sclerosis (ALS) is considered a “non-cell autonomous” process, with astrocytes playing a critical role in disease progression. Glial cells are activated early in transgenic mice expressing mutant SOD1, suggesting that neuroinflammation has a relevant role in the cascade of events that trigger the death of motor neurons. An inflammatory cascade including COX2 expression, secretion of cytokines and release of NO from astrocytes may descend from activation of a NF-κB-mediated pathway observed in astrocytes from ALS patients and in experimental models. We have attempted rescue of transgenic mutant SOD1 mice through the inhibition of the NF-κB pathway selectively in astrocytes. Here we show that despite efficient inhibition of this major pathway, double transgenic mice expressing the mutant SOD1G93A ubiquitously and the dominant negative form of IκBα (IκBαAA) in astrocytes under control of the GFAP promoter show no benefit in terms of onset and progression of disease. Our data indicate that motor neuron death in ALS cannot be prevented by inhibition of a single inflammatory pathway because alternative pathways are activated in the presence of a persistent toxic stimulus

Socio-demographic factors associated with pet ownership amongst adolescents from a UK birth cohort

Background: In developed nations, pet ownership is common within families. Both physical and psychological health benefits may result from owning a pet during childhood and adolescence. However, it is difficult to determine whether these benefits are due to pet ownership directly or to factors linked to both pet ownership and health. Previous research found associations between a range of socio-demographic factors and pet ownership in seven-year-old children from a UK cohort. The current study extends this research to adolescence, considering that these factors may be important to consider in future Human-Animal Interaction (HAI) research across childhood.Results:The Avon Longitudinal Study of Parents and Children (ALSPAC) collected pet ownership data prospectively via maternal reports from gestation up to age 10 years old and via self-report retrospectively at age 18 for ages 11(n= 3063) to 18 years old (n= 3098) on cats, dogs, rabbits, rodents, birds, fish, tortoise/turtles and horses. The dataset also contains a wide range of potential confounders, including demographic and socio-economic variables.The ownership of all pet types peaked at age 11 (80%) and then decreased during adolescence, with the exclusion of cats which remained constant (around 30%), and dogs which increased through 11–18 years (26–37%). Logistic regression was used to build multivariable models for ownership of each pet type at age 13 years, and the factors identified in these models were compared to previously published data for 7 year-olds in the same cohort. There was some consistency with predictors reported at age 7. Generally sex, birth order, maternal age, maternal education, number of people in the household, house type, and concurrent ownership of other pets were associated with pet ownership at both 7 and 13 years (the direction of association varied according to pet type).Factors that were no longer associated with adolescent pet ownership included child ethnicity, paternal education,and parental social class.Conclusions:A number of socio-demographic factors are associated with pet ownership in childhood and adolescence and they differ according to the type of pet, and age of child. These factors are potential confounders that must be considered in future HAI studies

EphA3 Expressed in the Chicken Tectum Stimulates Nasal Retinal Ganglion Cell Axon Growth and Is Required for Retinotectal Topographic Map Formation

BACKGROUND: Retinotopic projection onto the tectum/colliculus constitutes the most studied model of topographic mapping and Eph receptors and their ligands, the ephrins, are the best characterized molecular system involved in this process. Ephrin-As, expressed in an increasing rostro-caudal gradient in the tectum/colliculus, repel temporal retinal ganglion cell (RGC) axons from the caudal tectum and inhibit their branching posterior to their termination zones. However, there are conflicting data regarding the nature of the second force that guides nasal axons to invade and branch only in the caudal tectum/colliculus. The predominant model postulates that this second force is produced by a decreasing rostro-caudal gradient of EphA7 which repels nasal optic fibers and prevents their branching in the rostral tectum/colliculus. However, as optic fibers invade the tectum/colliculus growing throughout this gradient, this model cannot explain how the axons grow throughout this repellent molecule. METHODOLOGY/PRINCIPAL FINDINGS: By using chicken retinal cultures we showed that EphA3 ectodomain stimulates nasal RGC axon growth in a concentration dependent way. Moreover, we showed that nasal axons choose growing on EphA3-expressing cells and that EphA3 diminishes the density of interstitial filopodia in nasal RGC axons. Accordingly, in vivo EphA3 ectodomain misexpression directs nasal optic fibers toward the caudal tectum preventing their branching in the rostral tectum. CONCLUSIONS: We demonstrated in vitro and in vivo that EphA3 ectodomain (which is expressed in a decreasing rostro-caudal gradient in the tectum) is necessary for topographic mapping by stimulating the nasal axon growth toward the caudal tectum and inhibiting their branching in the rostral tectum. Furthermore, the ability of EphA3 of stimulating axon growth allows understanding how optic fibers invade the tectum growing throughout this molecular gradient. Therefore, opposing tectal gradients of repellent ephrin-As and of axon growth stimulating EphA3 complement each other to map optic fibers along the rostro-caudal tectal axis

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Global Transcriptome and Deletome Profiles of Yeast Exposed to Transition Metals

A variety of pathologies are associated with exposure to supraphysiological concentrations of essential metals and to non-essential metals and metalloids. The molecular mechanisms linking metal exposure to human pathologies have not been clearly defined. To address these gaps in our understanding of the molecular biology of transition metals, the genomic effects of exposure to Group IB (copper, silver), IIB (zinc, cadmium, mercury), VIA (chromium), and VB (arsenic) elements on the yeast Saccharomyces cerevisiae were examined. Two comprehensive sets of metal-responsive genomic profiles were generated following exposure to equi-toxic concentrations of metal: one that provides information on the transcriptional changes associated with metal exposure (transcriptome), and a second that provides information on the relationship between the expression of ∼4,700 non-essential genes and sensitivity to metal exposure (deletome). Approximately 22% of the genome was affected by exposure to at least one metal. Principal component and cluster analyses suggest that the chemical properties of the metal are major determinants in defining the expression profile. Furthermore, cells may have developed common or convergent regulatory mechanisms to accommodate metal exposure. The transcriptome and deletome had 22 genes in common, however, comparison between Gene Ontology biological processes for the two gene sets revealed that metal stress adaptation and detoxification categories were commonly enriched. Analysis of the transcriptome and deletome identified several evolutionarily conserved, signal transduction pathways that may be involved in regulating the responses to metal exposure. In this study, we identified genes and cognate signaling pathways that respond to exposure to essential and non-essential metals. In addition, genes that are essential for survival in the presence of these metals were identified. This information will contribute to our understanding of the molecular mechanism by which organisms respond to metal stress, and could lead to an understanding of the connection between environmental stress and signal transduction pathways

Global Patterns and Controls of Nutrient Immobilization On Decomposing Cellulose In Riverine Ecosystems

Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature