1,721,090 research outputs found
COX-2 inhibition induces autophagic flux and influences extracellular vesicle profile in human glioblastoma U87MG cell line
No full textIntroduction: Glioblastoma Multiforme (GBM), a lethal primary tumor of the central nervous system, is characterized by a highly infiltrating capacity, striking cellular heterogeneity, relapsing ability, and resistance to therapy. At present, the standard of therapeutic protocol consists of maximum conceivable surgical resection, followed by radiotherapy plus parallel adjuvant chemotherapy with temozolomide. Despite this, resistance to therapy limits its effectiveness, and GBM cannot be effectively controlled, being characterized by an extremely broad set of genetic and epigenetic alterations and high rates of recurrences. Several studies have suggested that gliomas, similar to most established malignant tumors, are characterized by a moderately inflammatory environment. Growing evidence over the past decades indicates the involvement of COX-2 in the progression of a variety of tumors, including GBM. We analyzed the effect of NS398, a COX-2 inhibitor, on the autophagic flux and extracellular vesicle (EV) secretion in the human U87MG glioma cell line. The effects of glioma stem cells (GSC)-derived EVs on adherent U87MG were also evaluated. Methods: After treatments, cell morphology was assessed by optical microscopy and by SEM. Cell proliferation and migration were examined using CCK-8 and scratch wound healing assay. Cell cycle profile and apoptosis were analyzed by flow cytometry. Autophagy-associated acidic vesicular organelles were quantified by acridine orange staining. A nanoparticle tracking analysis was used to assess the number and size of EVs. EV ultrastructure was verified by TEM and protein levels analyzed by WB. Acid sphingomyelinase was determined through ceramide levels. Results: NS398 was able to induce autophagy in both adherent U87MG and GSCs and EV secretion in GSCs. EVs secreted by NS398-treated GSC, but not those from untreated cells, were able to inhibit adherent U87MG cell growth and migration while also inducing a consistent level of autophagy. Conclusions: The hypothesis of COX-2 expression as GBM profile marker or interesting therapeutic target is supported by our findings. Autophagy and EV release following treatment with the COX-2 inhibitor could represent useful elements to better understand the complex biomolecular frame of GBM
Ceramide and apoptosis
No full textAbstract
Ceramide is a sphingosine-based lipid second messeger molecule that is involved in regulation of differentiation, proliferation, apoptosis, or growth arrest. The pleiotropic nature of ceramide signalling may be due to the fact that it is linked to a variety of receptors in different cell types. Since the ceramide is one of the most hydrophobic molecules in mammalian cells, it tends to remain within the membrane bilayer and may exert its function exclusively at the subcellular site of production. Ceramide is generated from sphingomyelin (SM) by the action of several isoforms of SMase (neutral, acid and alkaline SMase) or by de novo synthesis co-ordinated through the enzyme ceramide synthase. In this chapter, the pathways of ceramide generation, the interaction of ceramide with several enzymes and apoptotic signalling cascades are describ
“Attività Natural Killer in splenociti e cellule mononucleate di sangue periferico di pollo”.
No full text
Association between salivary cortisol level and caries in early childhood
Full text linkThe present study aimed to evaluate the association between caries and oral health status, age, salivary cortisol levels, and parental education in children with and without prior dental caries experience. Methods An observational case-control study was performed including 122 children aged between 3 and 6 years who were clinically examined for caries experience using the sum of decayed, missing, and filled teeth in the primary (dmft index) and permanent (DMFT index) dentition. Oral health status was also evaluated using the Simplified Oral Hygiene index (OHI-S). Parents filled a questionnaire to provide information on other variables. Salivary cortisol levels were estimated 1 h after routine dental brushing. Results We found that dental caries experience was associated with cortisol level, plaque, age, and high calculus levels. High cortisol levels and age are important risk factors for caries development with odds ratios of 3.05 (95% CI: 1.84-5.06) and 1.59 (95% CI: 1.09-2.58), respectively. Multivariate logistic analysis showed that cortisol level and age were independently associated with caries presence. Caries experience was not associated with education of parents, feedinghygiene habits of child or birth events. Conclusion The present findings support the hypothesis that caries is mainly correlated with high salivary cortisol levels. Dental caries experience in children was also positively associated with tartar, plaque, and age. © 2018, Italian Society of Paediatric Dentistry
- …
