miRNA signature associated with R-CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma.

Refractoriness remains as one of the challenges in patients with lymphoma under chemotherapy, and among biological regulators in cells driving this type of response are microRNAs (miRNAs). Different genes are constantly turned on or off according to the miRNAs expression profiles affecting the drug response in patients and their stability in serum and plasma makes them potential prognostic biomarkers in several diseases. Here we described a profile of miRNAs in plasma of diffuse large B cell lymphoma (DLBCL) patients. miRNA expression arrays were carried using pre-treatment plasma samples of sixteen patients, followed by a comparison between the responder and the non-responders. After six cycles of R-CHOP treatment, twelve out of sixteen patients were clinically diagnosed with complete response while in four patients no clinical response was observed. Between these groups, a signature of fifteen differential expressed miRNAs was found. The circulating miRNAs in plasma of patients with no response were related to the drug resistance in other types of cancer, by targeting genes involved in cell proliferation and apoptosis, among other cell processes.

The cut-off effect of n-alcohols in lipid rafts: A lipid-dependent phenomenon☆.

n-Aliphatic alcohols act as anesthetics only up to a certain chain length, beyond which its biological activity disappears. This is known as the 'cut-off' phenomenon. Although the most accepted explanation is based on action sites in membrane proteins, it is not well understood why alcohols alter their functions. The structural dependence of these protein receptors to lipid domains known as 'lipid rafts', suggests a new approach to tackle the puzzling phenomenon. In this work, by performing molecular dynamic simulations (MDS) to explore the lipid role, we provide relevant molecular details about the membrane-alcohol interaction at the cut-off point regime. Since the high variability of the cut-off points found on protein receptors in neurons may be a consequence of differences in the lipid composition surrounding such proteins, our results could have a clear-cut importance.

The interaction of local anesthetics with lipid membranes.

Molecular Dynamic Simulations are performed to evaluate the interaction of lidocaine, procaine and tetracaine with a lipid membrane. The main interest is to evaluate the structural changes produced by these local anesthetics in the bilayers. Penetration trajectories, interaction energies, entropy changes and an order parameter are calculated to quantify the destabilization of the lipid configurations. We show that such structural parameters give important information to understand how anesthetic agents influence the structure of plasma membranes. Graphic processing units (GPUs) are used in our simulations.