<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Gratton, Rossella</style></author><author><style face="normal" font="default" size="100%">Tricarico, Paola Maura</style></author><author><style face="normal" font="default" size="100%">Guimarães, Rafael Lima</style></author><author><style face="normal" font="default" size="100%">Celsi, Fulvio</style></author><author><style face="normal" font="default" size="100%">Crovella, Sergio</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Lopinavir/Ritonavir Treatment Induces Oxidative Stress and Caspaseindependent Apoptosis in Human Glioblastoma U-87 MG Cell Line.</style></title><secondary-title><style face="normal" font="default" size="100%">Curr HIV Res</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Curr. HIV Res.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">16</style></volume><pages><style face="normal" font="default" size="100%">106-112</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Lopinavir and Ritonavir (LPV/r) treatment is widely used to prevent HIV mother-to-child transmission. Nevertheless, studies related to the impact of these compounds on patients, in particular in the foetus and newborns, are strictly required due to the controversial findings reported in the literature concerning possible neurologic side effects following the administration of these drugs.&lt;/p&gt;&lt;p&gt;&lt;b&gt;OBJECTIVES: &lt;/b&gt;In our study, we evaluated the impact of LPV/r treatment on the human glioblastoma U- 87 MG cell line.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;In order to evaluate the influence of Lopinavir and Ritonavir in terms of oxidative stress (ROS production), mitochondrial morphology and apoptotic cell death, the latter either in the presence or in the absence of caspase-3 and -9 inhibitors, we treated U-87 MG with increasing doses (0.1-1-10-25-50 µM) of Lopinavir and Ritonavir for 24h, either in single formulation or in combination. ROS production was measured by flow cytometry using H2DCFDA dye, mitochondrial morphology was evaluated using MitoRed dye and apoptotic cell death was monitored by flow cytometry using Annexin V-FITC and Propidium Iodide.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;We observed that co-treatment with Lopinavir and Ritonavir (25 and 50 µM) promoted a significant increase in ROS production, caused mitochondrial network damage and induced apoptosis in a caspase-independent manner.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSION: &lt;/b&gt;Based on our findings, concordant with others reported in the literature, we hypothesize that LPV/r treatment could not be entirely free from side effects, being aware of the need of validation in in vivo models, necessary to confirm our results.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/29804534?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tricarico, Paola Maura</style></author><author><style face="normal" font="default" size="100%">Romeo, Alessandra</style></author><author><style face="normal" font="default" size="100%">Gratton, Rossella</style></author><author><style face="normal" font="default" size="100%">Crovella, Sergio</style></author><author><style face="normal" font="default" size="100%">Celsi, Fulvio</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Lack of Prenylated Proteins, Autophagy Impairment and Apoptosis in SH-SY5Y Neuronal Cell Model of Mevalonate Kinase Deficiency.</style></title><secondary-title><style face="normal" font="default" size="100%">Cell Physiol Biochem</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Cell. Physiol. Biochem.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Autophagy</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line, Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">Macrolides</style></keyword><keyword><style  face="normal" font="default" size="100%">Mevalonate Kinase Deficiency</style></keyword><keyword><style  face="normal" font="default" size="100%">Microtubule-Associated Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Models, Biological</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Phosphotransferases (Alcohol Group Acceptor)</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Prenylation</style></keyword><keyword><style  face="normal" font="default" size="100%">Rats</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">41</style></volume><pages><style face="normal" font="default" size="100%">1649-1660</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND/AIMS: &lt;/b&gt;Mevalonate Kinase Deficiency (MKD), is a hereditary disease due to mutations in mevalonate kinase gene (MVK). MKD has heterogeneous clinical phenotypes: the correlation between MVK mutations and MKD clinical phenotype is still to be fully elucidated. Deficiency of prenylated proteins has been hypothesized as possible MKD pathogenic mechanism. Based on this hypothesis and considering that neurologic impairment characterizes Mevalonic Aciduria (MA), the most severe form of MKD, we studied the effects of I268T and N301T MVK mutations on protein prenylation, autophagy and programmed cell death in SH-SY5Y neuroblastoma cell lines.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;SH-SY5Y cells were transiently transfected, with the pCMV-6 plasmid containing MVK wild type and the two mutated sequences. Protein prenylation levels were evaluated using GFP-RhoA-F to assess farnesylation, and GFP-RhoA to evaluate geranylgeranylation; autophagy was measured by evaluating LC3 and p62 protein levels, while Annexin V-FITC and Propidium Iodide staining allowed apoptosis detection.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;MVK mutants' over-expression causes decreased levels of farnesylation and geranylgeranylation, and also increased LC3 lipidation in SH-SY5Y, with concomitant p62 accumulation. Treatment with bafilomycin A1 (an inhibitor of vacuolar H+-ATPase, a late autophagy inhibitor) further increase LC3-II and p62 levels, suggesting that degradation of autophagolysosome could be impaired. SH-SY5Y, with both MVK mutants, showed apoptosis increase; the presence of N301T associated with augmented cell death.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;We hypothesize that mevalonate pathway impairment causes alteration of farnesylation and geranylgeranylation proteins and alteration of the autophagic flux; these changes can induce apoptosis, possibly more relevant in the presence of N301T mutation.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">4</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/28359055?dopt=Abstract</style></custom1></record></records></xml>