Erratum: Proof-of-concept study for liver-directed miQURE technology in a dyslipidemic mouse model.

[This corrects the article DOI: 10.1016/j.omtn.

Proof-of-concept study for liver-directed miQURE technology in a dyslipidemic mouse model.

A gene-silencing platform (miQURE) has been developed and successfully used to deliver therapeutic microRNA (miRNA) to the brain, reducing levels of neurodegenerative disease-causing proteins/RNAs via RNA interference and improving the disease phenotype in animal models. This study evaluates the use of miQURE technology to deliver therapeutic miRNA for liver-specific indications. Angiopoietin-like 3 () was selected as the target mRNA because it is produced in the liver and because loss-of-function mutations and/or pharmacological inhibition of ANGPTL3 protein lowers lipid levels and reduces cardiovascular risk.

DNA elements for constitutive androstane receptor- and pregnane X receptor-mediated regulation of bovine CYP3A28 gene.

The regulation of cytochrome P450 3A (CYP3A) enzymes is established in humans, but molecular mechanisms of its basal and xenobiotic-mediated regulation in cattle are still unknown. Here, ~10 kbp of the bovine CYP3A28 gene promoter were cloned and sequenced, and putative transcription factor binding sites were predicted. The CYP3A28 proximal promoter (PP; -284/+71 bp) contained DNA elements conserved among species.

Significance of the goby Zosterisessor ophiocephalus as a sentinel species for Venice Lagoon contamination: Combining biomarker responses and bioaccumulation.

The Venice Lagoon is an interesting example of an ecosystem suffering for a considerable anthropogenic impact, resulting in high concentrations of persistent organic pollutants (POPs) in lagoon sediments and seafood. In this context, biomonitoring is a crucially important task. The present study aimed at evaluating the validity of a multiple biomarker approach in a benthic fish species.

Characterization of ligand-dependent activation of bovine and pig constitutive androstane (CAR) and pregnane X receptors (PXR) with interspecies comparisons.

1. Nuclear receptors CAR (NR1I3) and PXR (NR1I2) are major ligand-activated transcriptional regulators of xenobiotic metabolism and disposition and modulators of endobiotic metabolism. Differences in xenobiotic selectivity between the human and rodent receptors are well recognized but there is lack of such information on properties of CAR and PXR in important domestic animals.

Feline intestinal mast cell tumours: clinicopathological characterisation and KIT mutation analysis.

Objectives: Feline intestinal mast cell tumours (FIMCTs) are rare and reportedly characterised by poor differentiation, aggressive biological behaviour and lack of reliable therapeutic aids. KIT proto-oncogene-activating mutations have never been investigated in these tumours. This study describes the main clinicopathological and microscopic features observed in 17 FIMCTs.

Absolute quantification and modulation of cytochrome P450 3A isoforms in cattle liver.

In humans and laboratory animals, knowledge about cytochrome P450 (CYP) regulation and function is detailed and very extensive. However, CYPs have still been incompletely characterized in veterinary species so far. In this study, mRNA levels of three CYP3A enzymes (CYP3A28, CYP3A38 and CYP3A48) were measured in cattle liver by using quantitative real-time RT-PCR (qPCR) assays and an absolute quantification approach.

Tissue distribution and phenobarbital induction of target SLC- and ABC- transporters in cattle.

In veterinary pharmaco-toxicological sciences, few data about uptake and efflux drug transporters (DTs) expression and regulation phenomena have been published. In this study, the tissue distribution and transcriptional modulation of solute carrier (SLC) and ATP-binding cassette (ABC) DTs were investigated in cattle orally administered with phenobarbital (PB) by using a quantitative real-time RT-PCR approach. The criterion for target gene selection was the PB-responsiveness in human and rodent model species.

Primary hepatocytes as an useful bioassay to characterize metabolism and bioactivity of illicit steroids in cattle.

Cattle hepatocytes have already been used in veterinary in vitro toxicology, but their usefulness as a multi-parametric screening bioassay has never been investigated so far. In this study, cattle hepatocytes were incubated with illicit steroids/prohormones (boldenone, BOLD; its precursor boldione, ADD; dehydroepiandrosterone, DHEA; an association of ADD:BOLD), to characterize their transcriptional effects on drug metabolizing enzymes (DMEs) and related nuclear receptors (NRs), on cytochrome P450 3A (CYP3A) apoprotein and catalytic activity as well as to determine ADD and BOLD metabolite profiling. DHEA-exposed cells showed an up-regulation (higher than 2.

Constitutive expression and phenobarbital modulation of drug metabolizing enzymes and related nuclear receptors in cattle liver and extra-hepatic tissues.

In humans and rodents, phenobarbital (PB) induces hepatic and extra-hepatic drug metabolizing enzymes (DMEs) through the activation of specific nuclear receptors (NRs). In contrast, few data about PB transcriptional effects in veterinary species are available. The constitutive expression and modulation of PB-responsive NR and DME genes, following an oral PB challenge, were investigated in cattle liver and extra-hepatic tissues (duodenum, kidney, lung, testis, adrenal and muscle).

Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases and vascular endothelial growth factor in canine mast cell tumours.

Degradation of the extracellular matrix and angiogenesis are associated with tumour invasion and metastasis in human and canine neoplasia. Matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and vascular endothelial growth factor-A (VEGF-A) are key mediators of these respective processes. Mast cell tumour (MCT) is the most common malignant cutaneous tumour in dogs.

Effects of time culture and prototypical cytochrome P450 3A (CYP3A) inducers on CYP2B22, CYP2C, CYP3A and nuclear receptor (NR) mRNAs in long-term cryopreserved pig hepatocytes (CPHs).

In the present study, transcriptional and post-translational effects of culturing time and prototypical cytochrome P450 3A (CYP3A) inducers on principal nuclear receptors (NRs), CYP2B22, 2C and 3A were investigated in long-term stored (~10 years) cryopreserved pig hepatocytes (CPHs). In the time-course study, a crush and rise effect was observed for pregnane X receptor (NR1I2) and constitutive androstane receptor (NR1I3) mRNAs, while a time-dependent increase of retinoid X receptor alpha (NR2B1) was noticed. Cytochrome P450 gene expression profiles were down-regulated as a function of time.

Matrix metalloproteinases and their inhibitors in canine mammary tumors.

Background: Malignant canine mammary tumors represent 50% of all neoplasms in female dogs. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be involved in tumor progression, and they are also associated with the reactive stroma, which provides structural and vascular support for tumor growth.

Results: MMP-2, MMP-9 and MT1-MMP were expressed at both the mRNA and protein levels in tumor samples.

Steroidogenic enzyme gene expression profiles in the testis of cattle treated with illicit growth promoters.

Recently, the effect of illicit growth promoters (GPs) upon the cattle transcriptome has drawn the increasing attention of the scientific community. In the present study, the pre-transcriptional effects of three different illicit protocols on a set of target genes, including steroidogenic enzymes and three related transcription factors, were estimated in cattle testis. Beef cattle were administered with dexamethasone (DEX) orally (group D(1)) or intramuscularly in experiment 1 (group DIM).

Proposed new nomenclature for Bos taurus cytochromes P450 involved in xenobiotic drug metabolism.

The cytochrome P450 (CYP) superfamily of drug metabolizing enzymes (DMEs) plays a central role in the oxidative metabolism of xenobiotics to which living organisms are exposed. In Bos taurus (cattle), a definitive nomenclature for CYP proteins is still lacking, and to unambiguously settle cattle nomenclature a phylogenetic analysis of proteins belonging to CYP 1-4 families was performed. Sequences collected from GenBank and Dr Nelson's P450 homepage databases were analyzed according to the maximum likelihood method.

Constitutive expression of drug metabolizing enzymes and related transcription factors in cattle testis and their modulation by illicit steroids.

In veterinary species, little information about extrahepatic drug metabolism is actually available. Therefore, the presence of foremost drug metabolizing enzymes (DMEs) and related transcription factors mRNAs was initially investigated in cattle testis; then, their possible modulation following the in vivo exposure to illicit growth promoters (GPs), which represent a major issue in cattle farming, was explored. All target genes were expressed in cattle testis, albeit to a lower extent compared to liver ones; furthermore, illicit protocols containing dexamethasone and 17β-oestradiol significantly up-regulated cytochrome P450 1A1, 2E1, oestrogen receptor-α and peroxisome proliferator-activated receptor-α mRNA levels.

Effects of illicit dexamethasone upon hepatic drug metabolizing enzymes and related transcription factors mRNAs and their potential use as biomarkers in cattle.

In cattle fattening, the illicit use of growth promoters (GPs) represents a major problem. The synthetic corticosteroid dexamethasone (DEX) is the GP mostly used, alone or in combination with other steroids or beta-agonists. Recently, GPs were shown to disrupt some cattle cytochromes P450 (CYPs) at the post-transcriptional level; therefore, the effects of two illicit protocols containing DEX (alone or together with 17beta-estradiol, 17betaE) upon main cattle liver drug metabolizing enzymes (DMEs) mRNAs and related transcription factors were investigated by quantitative real time RT-PCR.