PEROXYNITRITE IS INVOLVED IN THE MITOCHONDRIAL DYSFUNCTION INDUCED BY SORAFENIB IN LIVER CANCER CELLS.

Background: Sorafenib is a tyrosine kinase inhibitor (TKI) that belongs to the landscape of treatments for advanced stages of hepatocellular carcinoma (HCC). The induction of cell death and cell cycle arrest by Sorafenib has been associated with mitochondrial dysfunction in liver cancer cells. Our research aim was to decipher underlying oxidative and nitrosative stress induced by Sorafenib leading to mitochondrial dysfunction in liver cancer cells.

Adverse effects of environmentally relevant concentration of microplastics on gill epithelium permeability in the euryhaline Mediterranean killifish Aphanius fasciatus.

Estuaries and lagoons are characterized by fluctuating salinity and significant amounts of microplastics (MPs) and are increasingly subjected to various anthropogenic pressures. We investigated whether the accumulation of MPs in the gills of fish inhabiting these fragile ecosystems alters osmoregulation and, consequently, their ability to tolerate fluctuating salinity. The effects of a 15-day exposure to an environmentally relevant concentration (20 μg/L) of spherical polystyrene microplastics (PS-MPs) with a diameter of 5 μm were assessed in the Mediterranean killifish Aphanius fasciatus, focusing on tissue and gene expression changes related to factors of paracellular and transcellular permeability of the gill epithelium during the transition from seawater to freshwater.

Biomonitoring emerging hazards of pharmaceuticals in river water using gut microbiome and behavioural Daphnia magna responses.

A cost-effective Daphnia magna testing framework was applied to identify emerging hazards such as neurological and cardiovascular defects as well as antibiotic resistant genes (ARGs), related to pharmaceuticals present in waste water treated (WWTP) effluent discharged into rivers. D. magna juveniles were exposed during 48 h to water samples from three rivers in the vicinity of Barcelona (NE Spain), Besós, Llobregat and Onyar, upstream and downstream of WWTP discharging points.

Efficient removal of antibiotic resistance genes and of enteric bacteria from reclaimed wastewater by enhanced Soil Aquifer Treatments.

Soil Aquifer Treatment (SAT) is a robust technology to increase groundwater recharge and to improve reclaimed water quality. SAT reduces dissolved organic carbon, contaminants of emerging concern, nutrients, and colloidal matter, including pathogen indicators, but little is known about its ability to reduce loads of antibiotic resistance genes (ARGs) from reclaimed waters. Here we test six pilot SAT systems to eliminate various biological hazards from the secondary effluents of a wastewater treatment plant (WWTP), equipped with reactive barriers (RBs) including different sorptive materials.

Predictive factors for decompensating events in patients with cirrhosis with primary biliary cholangitis under different lines of therapy.

Background And Aims: The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients.

Efficient removal of toxicity associated to wastewater treatment plant effluents by enhanced Soil Aquifer Treatment.

The regeneration of wastewater has been recognized as an effective strategy to counter water scarcity. Nonetheless, Wastewater Treatment Plant (WWTP) effluents still contain a wide range of contaminants of emerging concern (CECs) even after water depuration. Filtration through Soil Aquifer Treatment (SAT) systems has proven efficient for CECs removal although the attenuation of their associated biological effects still remains poorly understood.

Emergency department contribution to HCV elimination in the Iberian Peninsula.

Background: Undiagnosed cases of hepatitis C virus (HCV) infection result in significant morbidity and mortality, further transmission, and increased public health costs. Testing in emergency departments (EDs) is an opportunity to expand HCV screening. The goal of this project was to increase the proportion of eligible patients screened for HCV in urban areas.

Evolution of microbiome composition, antibiotic resistance gene loads, and nitrification during the on-farm composting of the solid fraction of pig slurry using two bulking agents.

Composting is a nature-based method used to stabilize organic matter and to transform nitrogen from animal farm manure or solid fraction of slurry (SFS). The use of composted material as source of nutrients for agriculture is limited by its potential to facilitate the propagation of biological hazards like pathogens and antibiotic-resistant bacteria and their associated antibiotic-resistance genes (ARG). We show here an experimental on-farm composting (one single batch) of pig SFS, performed under realistic conditions (under dry continental Mediterranean climate) for 280 days, and using two different bulking agents (maize straw and tree pruning residues) for the initial mixtures.

Non-regulated haloaromatic water disinfection byproducts act as endocrine and lipid disrupters in human placental cells.

The disinfection of drinking water generates hundreds of disinfection byproducts (DBPs), including haloaromatic DBPs. These haloaromatic DBPs are suspected to be more toxic than haloaliphatic ones, and they are currently not regulated. This work investigates their toxicity and ability to interfere with estrogen synthesis in human placental JEG-3 cells, and their genotoxic potential in human alveolar A549 cells.

Advances in Understanding the Role of NRF2 in Liver Pathophysiology and Its Relationship with Hepatic-Specific Cyclooxygenase-2 Expression.

Oxidative stress and inflammation play an important role in the pathophysiological changes of liver diseases. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that positively regulates the basal and inducible expression of a large battery of cytoprotective genes, thus playing a key role in protecting against oxidative damage. Cyclooxygenase-2 (COX-2) is a key enzyme in prostaglandin biosynthesis.

Impact of the antibiotic doxycycline on the D. magna reproduction, associated microbiome and antibiotic resistance genes in treated wastewater conditions.

Wastewater Treatment Plant (WWTP) effluents are important sources of antibiotics, antibiotic resistance genes (ARGs) and resistant bacteria that threaten aquatic biota and human heath. Antibiotic effects on host-associated microbiomes, spread of ARGs and the consequences for host health are still poorly described. This study investigated changes of the Daphnia magna associated microbiome exposed to the recalcitrant antibiotic doxycycline under artificial reconstituted lab water media (lab water) and treated wastewater media.

Combined toxic effects of cadmium and environmental microplastics in Aphanius fasciatus (Pisces, Cyprinodontidae).

Microplastics (MPs), plastic particles smaller than 5 mm in diameter, have received extensive attention as new environmental pollutants with still unexplored potential ecological risks. The main objective of the present study is to see if the concomitant exposure to MPs and Cd is more toxic than that to MPs or Cd separately in Aphanius fasciatus. Immature female were exposed to Cd and/or MPs for 21 days, and the subsequent effects were monitored by a combination of biochemical, histological and molecular toxicity markers.

Genotoxicity and endocrine disruption potential of haloacetic acids in human placental and lung cells.

Chlorination of water results in the formation of haloacetic acids (HAAs) as major disinfection byproducts (DBPs). Previous studies have reported some HAAs species to act as cytotoxic, genotoxic, and carcinogenic. This work aimed at further exploring the toxicity potential of the most investigated HAAs (chloroacetic (CAA), bromoacetic (BAA), iodoacetic (IAA) acid) and HAAs species with high content of bromine (tribromoacetic acid (TBAA)), and iodine in their structures (chloroiodoacetic (CIAA) and diiodoacetic acid (DIAA)) to human cells.

Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study.

Unlabelled: There is uncertainty regarding Wilson's disease (WD) management.

Objectives: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers.

Methods: Data on WD patients followed at 32 Spanish hospitals were collected.

Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes.

The biochemical mechanisms of cell injury and myocardial cell death after myocardial infarction remain unresolved. Cyclooxygenase 2 (COX-2), a key enzyme in prostanoid synthesis, is expressed in human ischemic myocardium and dilated cardiomyopathy, but it is absent in healthy hearts. To assess the role of COX-2 in cardiovascular physiopathology, we developed transgenic mice that constitutively express functional human COX-2 in cardiomyocytes under the control of the α-myosin heavy chain promoter.

COX-2 Expression in Hepatocytes Improves Mitochondrial Function after Hepatic Ischemia-Reperfusion Injury.

Cyclooxygenase 2 (COX-2) is a key enzyme in prostanoid biosynthesis. The constitutive hepatocyte expression of COX-2 has a protective role in hepatic ischemia-reperfusion (I/R) injury (IRI), decreasing necrosis, reducing reactive oxygen species (ROS) levels, and increasing autophagy and antioxidant and anti-inflammatory response. The physiopathology of IRI directly impacts mitochondrial activity, causing ATP depletion and being the main source of ROS.

A Very Rare Variant in , a Possible Cause of Hypercholesterolemia and Increased Glycemic Levels.

Patients with high cholesterol and glucose levels are at high risk for cardiovascular disease. The Sterol Regulatory Element Binding Protein (SREBP) system regulates genes involved in lipid, cholesterol and glucose pathways. Autosomal Dominant Hypercholesterolemias (ADHs) are a group of diseases with increased cholesterol levels.

Toxicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in early development: A wide-scope metabolomics assay in zebrafish embryos.

The tobacco-specific nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic and ubiquitous environmental pollutant for which toxic activity has been thoroughly investigated in murine models and human tissues. However, its potential deleterious effects on vertebrate early development are yet poorly understood. In this work, we characterized the impact of NNK exposure during early developmental stages of zebrafish embryos, a known alternative model for mammalian toxicity studies.

Smaug1 membrane-less organelles respond to AMPK and mTOR and affect mitochondrial function.

Smaug is a conserved translational regulator that binds numerous mRNAs, including nuclear transcripts that encode mitochondrial enzymes. Smaug orthologs form cytosolic membrane-less organelles (MLOs) in several organisms and cell types. We have performed single-molecule fluorescence in situ hybridization (FISH) assays that revealed that SDHB and UQCRC1 mRNAs associate with Smaug1 bodies in U2OS cells.