Search results for "NEUROSCIENCE"

Expression of regulatory genes in the embryonic brain of a lizard and implications for understanding pallial organization and evolution

2017

The comparison of gene expression patterns in the embryonic brain of mouse and chicken is being essential for understanding pallial organization. However, the scarcity of gene expression data in reptiles, crucial for understanding evolution, makes it difficult to identify homologues of pallial divisions in different amniotes. We cloned and analyzed the expression of the genes Emx1, Lhx2, Lhx9, and Tbr1 in the embryonic telencephalon of the lacertid lizard Psammodromus algirus. The comparative expression patterns of these genes, critical for pallial development, are better understood when using a recently proposed six-part model of pallial divisions. The lizard medial pallium, expressing all…

The role of Plasma Membrane Calcium ATPases (PMCAs) in neurodegenerative disorders

2017

Selective degeneration of differentiated neurons in the brain is the unifying feature of neurodegenerative disorders such as Parkinson's disease (PD) or Alzheimer's disease (AD). A broad spectrum of evidence indicates that initially subtle, but temporally early calcium dysregulation may be central to the selective neuronal vulnerability observed in these slowly progressing, chronic disorders. Moreover, it has long been evident that excitotoxicity and its major toxic effector mechanism, neuronal calcium overload, play a decisive role in the propagation of secondary neuronal death after acute brain injury from trauma or ischemia. Under physiological conditions, neuronal calcium homeostasis is…

The route to solve the interplay between inflammation, angiogenesis and anti-cancer immune response.

2016

Even though the crucial role played by inflammation in cancer development and progression was first hypothesized by Rudolf Virchow at the beginning of the nineteenth century, only recently inflammation has been recognized as a hallmark of cancer. At present, the biology underlying the humoral and cellular immune-suppressive cancer-associated inflammatory microenvironment is an active area of preclinical and clinical investigation.1, 2 Indeed, the possibility to modulate the inflammatory/immune microenvironment, by either antagonizing the tumor-associated immune-suppression or by enhancing the pre-existing anti-cancer immune response in tumor tissues, is a promising therapeutic option for ca…

Oxidative stress preconditioning of mouse perivascular myogenic progenitors selects a subpopulation of cells with a distinct survival advantage in vi…

2018

AbstractCell engraftment, survival and integration during transplantation procedures represent the crux of cell-based therapies. Thus, there have been many studies focused on improving cell viability upon implantation. We used severe oxidative stress to select for a mouse mesoangioblast subpopulation in vitro and found that this subpopulation retained self-renewal and myogenic differentiation capacities while notably enhancing cell survival, proliferation and migration relative to unselected cells. Additionally, this subpopulation of cells presented different resistance and recovery properties upon oxidative stress treatment, demonstrating select advantages over parental mesoangioblasts in …

Corrigendum: Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine mod…

2017

Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner…

MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells.

2018

AbstractMir-205 plays an important role in epithelial biogenesis and in mammary gland development but its role in cancer still remains controversial depending on the specific cellular context and target genes. We have previously reported that miR-205-5p is upregulated in breast cancer stem cells targeting ERBB pathway and leading to targeted therapy resistance. Here we show that miR-205-5p regulates tumorigenic properties of breast cancer cells, as well as epithelial to mesenchymal transition. Silencing this miRNA in breast cancer results in reduced tumor growth and metastatic spreading in mouse models. Moreover, we show that miR-205-5p knock-down can be obtained with the use of specific lo…

HMG-CoA reductase promotes protein prenylation and therefore is indispensible for T-cell survival.

2017

AbstractStatins are a well-established family of drugs that lower cholesterol levels via the competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). In addition, the pleiotropic anti-inflammatory effects of statins on T cells make them attractive as therapeutic drugs in T-cell-driven autoimmune disorders. Since statins do not exclusively target HMGCR and thus might have varying effects on different cell types, we generated a new mouse strain allowing for the tissue-specific deletion of HMGCR. Deletion of HMGCR expression in T cells led to a severe decrease in their numbers with the remaining cells displaying an activated phenotype, with an increased pro…

Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis

2016

Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppressed this production and induced cytotoxic effects in breast cancer stem-like cells, derived from dissociation of mammospheres. In particular, the drugs exerted a remarkable inhibitory effect on viability of stem-like cells. Such an effect was suppressed by N-acetylcysteine, suggesting a role of reactive oxygen species (ROS) generation in the cytotoxic effect. Instead z-VAD, a ge…

2017

AbstractPP2C serine–threonine phosphatase, Wip1, is an important regulator of stress response. Wip1 controls a number of critical cellular functions: proliferation, cell cycle arrest, senescence and programmed cell death, apoptosis or autophagy. Ppm1d, the gene encoding Wip1 phosphatase, is expressed in hematopoietic progenitors, stem cells, neutrophils, macrophages B and T lymphocytes in bone marrow and peripheral blood. The Wip1−/− mice display immunodeficiency, abnormal lymphoid histopathology in thymus and spleen, defects in B- and T-cell differentiation, as well as susceptibility to viral infection. At the same time, Wip1 knockout mice exhibit pro-inflammatory phenotype in skin and int…

Parthenolide prevents resistance of MDA-MB231 cells to doxorubicin and mitoxantrone: the role of Nrf2.

2017

Triple-negative breast cancer is a group of aggressive cancers with poor prognosis owing to chemoresistance, recurrence and metastasis. New strategies are required that could reduce chemoresistance and increases the effectiveness of chemotherapy. The results presented in this paper, showing that parthenolide (PN) prevents drug resistance in MDA-MB231 cells, represent a contribution to one of these possible strategies. MDA-MB231 cells, the most studied line of TNBC cells, were submitted to selection treatment with mitoxantrone (Mitox) and doxorubicin (DOX). The presence of resistant cells was confirmed through the measurement of the resistance index. Cells submitted to this treatment exhibit…