Proteomic biomarkers for survival in systemic sclerosis-associated pulmonary hypertension.

Background: Interstitial lung disease (ILD) and pulmonary hypertension (PH) represent the major causes of mortality in systemic sclerosis (SSc). Patients with systemic sclerosis and combined PH and ILD (SSc-PH-ILD) generally have a poor prognosis. Predictors of survival and of potential benefit of treatment are lacking in patients with SSc-PH-ILD.

Gene Therapy Strategy for Alzheimer's and Parkinson's Diseases Aimed at Preventing the Formation of Neurotoxic Oligomers in SH-SY5Y Cells.

We present here a gene therapy approach aimed at preventing the formation of Ca-permeable amyloid pore oligomers that are considered as the most neurotoxic structures in both Alzheimer's and Parkinson's diseases. Our study is based on the design of a small peptide inhibitor (AmyP53) that combines the ganglioside recognition properties of the β-amyloid peptide (Aβ, Alzheimer) and α-synuclein (α-syn, Parkinson). As gangliosides mediate the initial binding step of these amyloid proteins to lipid rafts of the brain cell membranes, AmyP53 blocks, at the earliest step, the Ca cascade that leads to neurodegeneration.

Functional, proteomic and phenotypic in vitro studies evidence podocyte injury after chronic exposure to heparin.

Unfractionated heparin (UFH) is a widely used anticoagulant that possess numerous properties including anti-inflammatory, anti-viral, anti-angiogenesis, and anti-metastatic effects. The effect of this drug was evaluated on the podocyte, an important actor of the glomerular filtration. Using a functional approach, we demonstrate that heparin treatment leads to a functional podocyte perturbation characterized by the increase of podocyte monolayer permeability.

Is the human model RPTEC/TERT1 a relevant model for assessing renal drug efflux?

Active tubular secretion plays a major role in renal excretion of drugs thanks to the presence of many membrane transporters such as ABC transporters. These proteins facilitate drug transfer into the urine and could be a source of pharmacokinetic variabilities. Up to now, several human in vitro models of proximal tubule have been proposed but few of them have been characterized for predicting drugs renal efflux.

Value of quantifying ABC transporters by mass spectrometry and impact on in vitro-to-in vivo prediction of transporter-mediated drug-drug interactions of rivaroxaban.

ABC transporters, such as P-gp and BCRP, are involved in rivaroxaban pharmacokinetics and can lead to drug-drug interactions (DDIs). Investigations of the victim role for rivaroxaban and transporter-mediated DDI are commonly performed using in vitro models. However, interpretation of rivaroxaban efflux transport and DDI studies in cell models may be influenced by P-gp and BCRP transporter abundance.