The xenobiotic transporter /MRP4 promotes epithelial mesenchymal transition in pancreatic cancer.

The xenobiotic transporter /MRP4 is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and correlates with a more aggressive phenotype and metastatic propensity. Here, we show that promotes epithelial-mesenchymal transition (EMT) in PDAC, a hallmark process involving the acquisition of mesenchymal traits by epithelial cells, enhanced cell motility, and chemoresistance. Modulation of levels in PANC-1 and BxPC-3 cell lines resulted in the dysregulation of genes present in the EMT signature.

Assessment of the environmental impacts associated with vineyards and winemaking. A case study in mountain areas.

Mountain wines produced in specific mountain areas and following singular practices have gained popularity over the last few decades. During this time, the environmental impacts associated with the food and beverage manufacturing sector have become a question of interest. However, the environmental impacts derived from the production of this peculiar wine have scarcely been studied until now.

Dopamine Receptor D1 Contributes to Cocaine Epigenetic Reprogramming of Histone Modifications in Male Germ Cells.

Paternal environmental perturbations, including cocaine intake, can affect the development and behavior of the offspring through epigenetic inheritance. However, the mechanism by which cocaine alters the male germ cells epigenome is almost unexplored. Here, we report that cocaine-treated male mice showed alterations on specific histone post-translational modifications (PTMs) including increased silent chromatin marks H3K9me3 and H3K27me3 and decreased active enhancer and promoter marks H3K27ac and H3K4me3 in isolated germ cells.

Analogues of the Lignan Pinoresinol as Novel Lead Compounds for P-glycoprotein (P-gp) Inhibitors.

To find novel P-gp-inhibitors, a library of pregnane X receptor (PXR) ligands and the ZINC DrugsNow library were superimposed on the P-gp inhibitor (+)-pinoresinol () used as a query for a three-dimensional similarity search. After determining the TanimotoCombo index of similarity with , eight compounds from the PXR library and two ZINC compounds were selected for biological evaluation. The P-gp inhibition study showed that compounds , , and successfully increased intracellular doxorubicin (DOX) accumulation in the P-gp overexpressed Lucena 1 cells from 25, 12.

Mechanism Underlying the Reversal of Drug Resistance in P-Glycoprotein-Expressing Leukemia Cells by Pinoresinol and the Study of a Derivative.

P-glycoprotein (P-gp) is a membrane protein associated with multidrug resistance (MDR) due to its key role in mediating the traffic of chemotherapeutic drugs outside cancer cells, leading to a cellular response that hinders efforts toward successful therapy. With the aim of finding agents that circumvent the MDR phenotype mediated by P-gp, 15 compounds isolated from native and naturalized plants of Argentina were screened. Among these, the non-cytotoxic lignan (±) pinoresinol successfully restored sensitivity to doxorubicin from 7 μM in the P-gp overexpressed human myelogenous leukemia cells, Lucena 1.

Diagnostic approach and management of occupational asthma by persulfate salts in a hairdresser.

An 18-year-old female hairdresser, nonsmoker and nonatopic, developed rhinoconjunctivitis followed by asthma after working for 18 months. The methods that were necessary to obtain a definitive diagnosis of occupational asthma are explained, as well as the medical management performed to improve her asthma over the next 12 months. Tryptase and eosinophil cationic protein (ECP) were determined before and after specific bronchial challenge.

Paracetamol (acetaminophen) hypersensitivity.

Background: Acetaminophen (paracetamol) is an analgesic antipyretic drug with no antiinflammatory effects and is widely used worldwide. Earlier clinical studies reported IgE-mediated adverse reactions to acetaminophen, but in vivo and in vitro tests have been inconclusive.

Objective: We propose to demonstrate an IgE-mediated mechanism in four patients with adverse reactions to acetaminophen (paracetamol).