| 1. |
- Bravi, Luca, et al.
(författare)
-
Endothelial Cells Lining Sporadic Cerebral Cavernous Malformation Cavernomas Undergo Endothelial-to-Mesenchymal Transition
- 2016
-
Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 47:3, s. 886-890
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Cerebral cavernous malformation (CCM) is characterized by multiple lumen vascular malformations in the central nervous system that can cause neurological symptoms and brain hemorrhages. About 20% of CCM patients have an inherited form of the disease with ubiquitous loss-of-function mutation in any one of 3 genes CCM1, CCM2, and CCM3. The rest of patients develop sporadic vascular lesions histologically similar to those of the inherited form and likely mediated by a biallelic acquired mutation of CCM genes in the brain vasculature. However, the molecular phenotypic features of endothelial cells in CCM lesions in sporadic patients are still poorly described. This information is crucial for a targeted therapy.METHODS: We used immunofluorescence microscopy and immunohistochemistry to analyze the expression of endothelial-to-mesenchymal transition markers in the cavernoma of sporadic CCM patients in parallel with human familial cavernoma as a reference control.RESULTS: We report here that endothelial cells, a cell type critically involved in CCM development, undergo endothelial-to-mesenchymal transition in the lesions of sporadic patients. This switch in endothelial phenotype has been described only in genetic CCM patients and in murine models of the disease. In addition, TGF-β/p-Smad- and β-catenin-dependent signaling pathways seem activated in sporadic cavernomas as in familial ones.CONCLUSIONS: Our findings support the use of common therapeutic strategies for both sporadic and genetic CCM malformations.
|
|
| 2. |
- Barcaccia, Barbara, et al.
(författare)
-
Mindfulness, Self-Compassion and Attachment: A Network Analysis of Psychopathology Symptoms in Adolescents
- 2020
-
Ingår i: Mindfulness. - : Springer Science and Business Media LLC. - 1868-8535 .- 1868-8527. ; 11, s. 2531-2541
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesMindfulness, positive self-related attitudes and secure attachment have been shown to protect against psychopathology during adolescence, but it is unknown how these factors are related to each other and which are most strongly linked to psychopathology symptoms.MethodsA cross-sectional research design was used with a large sample of adolescents (aged 14 to 18 years; n = 1660) that completed validated measures of mindfulness, self-related attitudes, attachment, depression, anxiety and anger. We employed network analytic methods in order to better understand associations among these variables.ResultsMindfulness was linked to lower levels of depression and anxiety while self-reassurance was linked to lower levels of anxiety and higher levels of anger. Self-hate was linked to depression. In turn, self-reassurance and self-hate were differentially linked to facets of attachment, particularly trust in parents.ConclusionsInterventions combining mindfulness practice and clinical techniques based on attachment theory, which operate on different psychological levels, may improve self-related attitudes, which in turn can help ameliorate depression and anxiety in adolescents. Alternatively, interventions directly targeting self-related attitudes, particularly self-reassurance and self-inadequacy, hold promise to achieve positive effects on mental health among adolescents.
|
|
| 3. |
- Sighel, Denise, et al.
(författare)
-
Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth
- 2021
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 35:4
-
Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma stem cells (GSCs) resist current glioblastoma (GBM) therapies. GSCs rely highly on oxidative phosphorylation (OXPHOS), whose function requires mitochondrial translation. Here we explore the therapeutic potential of targeting mitochondrial translation and report the results of high-content screening with putative blockers of mitochondrial ribosomes. We identify the bacterial antibiotic quinupristin/dalfopristin (Q/D) as an effective suppressor of GSC growth. Q/D also decreases the clonogenicity of GSCs in vitro, consequently dysregulating the cell cycle and inducing apoptosis. Cryoelectron microscopy (cryo-EM) reveals that Q/D binds to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis and functionally dysregulating OXPHOS complexes. These data suggest that targeting mitochondrial translation could be explored to therapeutically suppress GSC growth in GBM and that Q/D could potentially be repurposed for cancer treatment.
|
|
