Addition of grapes to both a standard and a high-fat Western pattern diet modifies hepatic and urinary metabolite profiles in the mouse.

The benefits of fruit and vegetable dietary consumption are largely defined in epidemiological terms. Relatively little is known about the discrete effects on metabolic pathways elicited by individual dietary fruits and vegetables. To address this, grape powder was added to both a standard and a high-fat Western pattern diet given to 10-week-old female C57BL/6J mice for a period of 91 days, whereupon 24 h urines were collected and the mice euthanized after a 12 h fast for the collection of liver tissue.

CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin.

Background: The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts.

Objectives: This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment.

Medication-enhanced behavior therapy for alcohol use disorder: Naltrexone, Alcoholics Anonymous Facilitation, and OPRM1 genetic variation.

Medication-assisted behavior treatment for alcohol use disorder (AUD) holds promise to enhance the efficacy of medication and of behavior therapy when administered individually. The present study examines the treatment benefit of combined outpatient naltrexone (NTX) treatment with Alcoholics Anonymous Facilitation (AAF) behavior therapy, in the context of OPRM1 genotype. The minor OPRM1 Asp40 G-allele has been associated with greater positive reinforcing effects of alcohol consumption and greater alcohol craving, suggesting that individuals carrying the OPRM1 G allele may have an improved naltrexone response.

Comparative analysis of the DYRK1A-SRSF6-TNNT2 pathway in myocardial tissue from individuals with and without Down syndrome.

Down syndrome (trisomy 21) is characterized by genome-wide imbalances that result in a range of phenotypic manifestations. Altered expression of DYRK1A in the trisomic context has been linked to some Down syndrome phenotypes. DYRK1A regulates the splicing of cardiac troponin (TNNT2) through a pathway mediated by the master splicing factor SRSF6.

Insights into the transcriptional regulation of the anthracycline reductase AKR7A2 in human cardiomyocytes.

Aldo-Keto Reductase Family 7 Member A2 (AKR7A2) is the most abundant anthracycline metabolizing enzyme in human myocardium. Myocardial AKR7A2 contributes to the synthesis of cardiotoxic C-13 anthracycline alcohol metabolites (e.g.

CBR1 rs9024 genotype status impacts the bioactivation of loxoprofen in human liver.

Loxoprofen is an anti-inflammatory drug that requires bioactivation into the trans-OH metabolite to exert pharmacological activity. Evidence suggests that carbonyl reductase 1 (CBR1) is important during the bioactivation of loxoprofen. This study examined the impact of the functional single nucleotide polymorphism CBR1 rs9024 on the bioactivation of loxoprofen in a collection of human liver samples.

Investigation of the role of DNA methylation in the expression of ERBB2 in human myocardium.

The ERBB2 gene encodes a transmembrane tyrosine kinase receptor that belongs to the epidermal growth factor receptor (EGFR) family. ERBB2 plays a pivotal role during heart development and is essential for normal cardiac function, particularly during episodes of cardiac stress. The monoclonal antibody drug trastuzumab is used for the therapy of breast cancers that overexpress ERBB2.

Transcriptional regulation of the canine carbonyl reductase 1 gene (cbr1) by the specificity protein 1 (Sp1).

The clinical use of anthracyclines to treat various canine cancers is limited by the development of cardiotoxicity. The intra-cardiac synthesis of anthracycline C-13 alcohol metabolites (e.g.

CELF4 Variant and Anthracycline-Related Cardiomyopathy: A Children's Oncology Group Genome-Wide Association Study.

Purpose: Interindividual variability in the dose-dependent association between anthracyclines and cardiomyopathy suggests that genetic susceptibility could play a role. The current study uses an agnostic approach to identify genetic variants that could modify cardiomyopathy risk.

Methods: A genome-wide association study was conducted in childhood cancer survivors with and without cardiomyopathy (cases and controls, respectively).

The Addiction-Related Gene Ankk1 is Oppositely Regulated by D1R- and D2R-Like Dopamine Receptors.

The ankyrin repeat and kinase domain containing 1 (ANKK1) TaqIA polymorphism has been extensively studied as a marker of the gene for dopamine receptor D2 (DRD2) in addictions and other dopamine-associated traits. In vitro mRNA and protein studies have shown a potential connection between ANKK1 and the dopaminergic system functioning. Here, we have investigated whether Ankk1 expression in the brain is regulated by treatment with dopaminergic agonists.

Role of DNA Methylation on the Expression of the Anthracycline Metabolizing Enzyme AKR7A2 in Human Heart.

The intracardiac synthesis of anthracycline alcohol metabolites by aldo-keto reductases (AKRs) contributes to the pathogenesis of anthracycline-related cardiotoxicity. AKR7A2 is the most abundant anthracycline reductase in hearts from donors with and without Down syndrome (DS), and its expression varies between individuals (≈tenfold). We investigated whether DNA methylation impacts AKR7A2 expression in hearts from donors with (n = 11) and without DS (n = 30).

Chromosome 21-derived hsa-miR-155-5p regulates mitochondrial biogenesis by targeting Mitochondrial Transcription Factor A (TFAM).

The regulation of mitochondrial biogenesis is under the control of nuclear genes including the master Mitochondrial Transcription Factor A (TFAM). Recent evidence suggests that the expression of TFAM is regulated by microRNAs (miRNAs) in various cellular contexts. Here, we show that hsa-miR-155-5p, a prominent miRNA encoded in chromosome 21, controls the expression of TFAM at the post-transcriptional level.

Analysis of mtDNA, miR-155 and BACH1 expression in hearts from donors with and without Down syndrome.

Cancer patients with Down syndrome (DS) are at increased risk for anthracycline-related cardiotoxicity. Mitochondrial DNA (mtDNA) alterations in hearts with-DS may contribute to anthracycline-related cardiotoxicity. Cardiac mtDNA and the mtDNA(4977) deletion were quantitated in samples with- (n = 11) and without-DS (n = 31).

Interindividual variability in the cardiac expression of anthracycline reductases in donors with and without Down syndrome.

Purpose: The intracardiac synthesis of anthracycline alcohol metabolites (e.g., daunorubicinol) contributes to the pathogenesis of anthracycline-related cardiotoxicity.

Expanding the synthesis of new trans-sulfonamide platinum complexes: cytotoxicity, SAR, fluorescent cell assays and stability studies.

In this manuscript, we describe the synthesis of new trans-N-sulfonamide platinum complexes and their antiproliferative activity (GI50, μM) in human solid tumors cells. The structure activity relationships (SAR), with different new synthesized complexes by variation in ligand, halogen and also in the stereochemistry of the ligand, has been studied. Solubility and stability studies have also been carried out as well as fluorescent cell assays in order to clarify the final target in the tumor cells.

The ANKK1 gene associated with addictions is expressed in astroglial cells and upregulated by apomorphine.

Background: TaqIA, the most widely analyzed genetic polymorphism in addictions, has traditionally been considered a gene marker for association with D2 dopamine receptor gene (DRD2). TaqIA is located in the coding region of the ANKK1 gene that overlaps DRD2 and encodes a predicted kinase ANKK1. The ANKK1 protein nonetheless had yet to be identified.

BAT1 promoter polymorphism is associated with rheumatoid arthritis susceptibility.

Objective: To analyze whether the polymorphisms -22 (G/C) and -348 (C/T) of the BAT1 gene are associated with susceptibility to rheumatoid arthritis (RA).

Methods: One hundred fifty-six patients with RA and 154 controls were genotyped for HLA-DRB1 and the polymorphisms -22 and -348 of the BAT1 gene.

Results: HLA-DRB1*04 alleles were associated with RA susceptibility (33.

Transcriptional regulation of ULBP1, a human ligand of the NKG2D receptor.

Tumor cells expressing ligands of the NKG2D receptor stimulate anti-tumor immunity mediated by natural killer and T cells. In humans, NKG2D ligands (NKG2DL) are encoded by MIC and ULBP proteins. NKG2DL exhibit highly restricted expression in healthy tissues but are widely expressed in tumors.