Aspirin-Mediated Reset of Preeclamptic Placental Stem Cell Transcriptome - Implication for Stabilized Placental Function.

Preeclampsia (PE) is a pregnancy-specific disease, occurring in ~ 2-10% of all pregnancies. PE is associated with increased maternal and perinatal morbidity and mortality, hypertension, proteinuria, disrupted artery remodeling, placental ischemia and reperfusion, and inflammation. The mechanism of PE pathogenesis remains unresolved explaining limited treatment. Aspirin is used to reduce the risk of developing PE. This study investigated aspirin\u27s effect on PE-derived placenta mesenchymal stem cells (P-MSCs). P-MSCs from chorionic membrane (CM), chorionic villi, membranes from the maternal and amniotic regions, and umbilical cord were similar in morphology, phenotype and multipotency. Since CM-derived P-MSCs could undergo long-term passages, the experimental studies were conducted with this source of P-MSCs. Aspirin (1 mM) induced significant functional and transcriptomic changes in PE-derived P-MSCs, similar to healthy P-MSCs. These include cell cycle quiescence, improved angiogenic pathways, and immune suppressor potential. The latter indicated that aspirin could induce an indirect program to mitigate PE-associated inflammation. As a mediator of activating the DNA repair program, aspirin increased p53, and upregulated genes within the basic excision repair pathway. The robust ability for P-MSCs to maintain its function with high dose aspirin contrasted bone marrow (M) MSCs, which differentiated with eventual senescence/aging with 100 fold less aspirin. This difference cautions how data from other MSC sources are extrapolated to evaluate PE pathogenesis. Dysfunction among P-MSCs in PE involves a network of multiple pathways that can be restored to an almost healthy functional P-MSC. The findings could lead to targeted treatment for PE

Discrimination of olive oil by cultivar, geographical origin and quality using potentiometric electronic tongue fingerprints

Legal regulations are set for protecting claims regarding olive oil geographical denomination. When meteorological or agroecological factors similarly affect different regions, the origin identification is a challenging task. This study demonstrated the use of a potentiometric electronic tongue coupled with linear discriminant analysis to discriminate the geographical origin of monovarietal Tunisian olive oil produced from local cv Chemlali (Kairouan, Sidi Bouzid or Sfax regions) and cv Sahli (Kairouan, Mahdia or Sousse regions). The potentiometric fingerprints of 12 or eight lipid sensors (for Chemlali and Sahli, respectively), selected using a simulated annealing meta-heuristic algorithm, allowed the correct prediction (repeated K-fold cross-validation) of the geographic production region with sensitivities of 92 ± 7% (Chemlali) and 97 ± 8% (Sahli). It was also confirmed the electronic tongue capability to classify Tunisian olive oil according to olive cultivar or quality grade. The results indicated the possible use of potentiometric fingerprints as a promising innovative strategy for olive oil analysis allowing assessing geographical origin, olive cultivar and quality grade, which are key factors determining olive oil price and consumers preference.This work was financially supported by Project POCI-01–0145-FEDER-006984 - Associate Laboratory LSRE-LCM, Project UID/QUI/00616/2013 - CQ-VR, and UID/AGR/00690/2013 - CIMO all funded by FEDER - Fundo Europeu de Desenvolvimento Regional through COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI) - and by national funds through FCT - Fundação para a Ciência e a Tecnologia, Portugal. Strategic funding of UID/BIO/04469/2013 unit is also acknowledged. Nuno Rodrigues thanks FCT, POPH-QREN and FSE for the Ph.D. Grant (SFRH/ BD/104038/2014). Souheib Oueslati is also grateful for the support of the Tunisian Ministry of Agriculture.info:eu-repo/semantics/publishedVersio

Human papillomavirus vaccine and systemic lupus erythematosus

To investigate the association between human papillomavirus (HPV) vaccination and autoimmune manifestations compatible with systemic lupus erythematosus (SLE) or SLE-like disease, the medical history of six women who presented with SLE or SLE-like disease following HPV immunization was collected. Data regarding type of vaccine, number of immunization, family and personal, clinical and serological features, as well as response to treatments were analyzed. In the reported cases, several common features were observed, such as personal or familial susceptibility to autoimmunity or adverse response to a prior dose of the vaccine, both of which may be associated with a higher risk of post-vaccination autoimmunity. Favorable response to immunosuppressant was observed in all patients. In the current study, a temporal association between immunization with HPV vaccine and the appearance of a spectrum of SLE-like conditions is reported. Additionally, among the patients described, several common features were observed that may enable better identification of subjects at risk. Further studies are required to assess the safety of immunization with the HPV vaccine in patients with autoimmune-rheumatic diseases or in subject at risk of autoimmunity as well as the potential beneficial effect of preventive immunosuppressants

Immune-mediated cerebellar ataxias: from bench to bedside

Abstract The cerebellum is a vulnerable target of autoimmunity in the CNS. The category of immune-mediated cerebellar ataxias (IMCAs) was recently established, and includes in particular paraneoplastic cerebellar degenerations (PCDs), gluten ataxia (GA) and anti-GAD65 antibody (Ab) associated-CA, all characterized by the presence of autoantibodies. The significance of onconeuronal autoantibodies remains uncertain in some cases. The pathogenic role of anti-GAD65Ab has been established both in vitro and in vivo, but a consensus has not been reached yet. Recent studies of anti-GAD65 Ab-associated CA have clarified that (1) autoantibodies are generally polyclonal and elicit pathogenic effects related to epitope specificity, and (2) the clinical course can be divided into two phases: a phase of functional disorder followed by cell death. These features provide the rationale for prompt diagnosis and therapeutic strategies. The concept “Time is brain” has been completely underestimated in the field of immune ataxias. We now put forward the concept “Time is cerebellum” to underline the importance of very early therapeutic strategies in order to prevent or stop the loss of neurons and synapses. The diagnosis of IMCAs should depend not only on Ab testing, but rather on a rapid and comprehensive assessment of the clinical/immune profile. Treatment should be applied during the period of preserved cerebellar reserve, and should encompass early removal of the conditions (such as remote primary tumors) or diseases that trigger the autoimmunity, followed by the combinations of various immunotherapies