GENE EXPRESSION TIME-SERIES ANALYSIS OF CAMPTHOTECIN EFFECTS IN U-87-MG AND DBTRG-05 GLIOBLASTOMA CELL LINES

The clinical efficacy of camptothecin (CPT), a drug specifically targetingtopoisomerase I (TopoI), is under evaluation for the treatment of malignant gliomas. Due to thehigh unresponsiveness of these tumours to chemotherapy, it would be very important to study thesignalling network that drives camptothecin outcome in this type of cancer cells. To address thisissue, we had previously compared the expression profile of human U87-MG glioblastoma cellswith that of a CPT-resistant counterpart, giving evidence that the development of a robustinflammatory response was the main transcriptional effect associated with CPT resistance.Here we report time-related changes and cell line specific patterns of gene expression after CPTtreatment by using two p53 wild-type glioblastoma cell lines, U87-MG and DBTRG-05, withdifferent sensitivities to TopoI inhibition

Supplementation with ribonucleotide-based ingredient (Ribodiet®) lessens oxidative stress, brain inflammation, and amyloid pathology in a murine model of Alzheimer

Abstract Alzheimer's disease (AD) is the most common type of dementia worldwide, characterized by the deposition of neurofibrillary tangles and amyloid-β (Aβ) peptides in the brain. Additionally, increasing evidence demonstrates that a neuroinflammatory state and oxidative stress, iron-dependent, play a crucial role in the onset and disease progression. Besides conventional therapies, the use of natural-based products represents a future medical option for AD treatment and/or prevention. We, therefore, evaluated the effects of a ribonucleotides-based ingredient (Ribodiet®) in a non-genetic mouse model of AD. To this aim, mice were injected intracerebroventricularly (i.c.v.) with Aβ1–42 peptide (3 µg/3 μl) and after with Ribodiet® (0.1–10 mg/mouse) orally (p.o.) 3 times weekly for 21 days following the induction of experimental AD. The mnemonic and cognitive decline was then evaluated, and, successively, we have assessed ex vivo the modulation of different cyto-chemokines on mice brain homogenates. Finally, the level of GFAP, S100β, and iron-related metabolic proteins were monitored as markers of reactive gliosis, neuro-inflammation, and oxidative stress. Results indicate that Ribodiet® lessens oxidative stress, brain inflammation, and amyloid pathology via modulation of iron-related metabolic proteins paving the way for its rationale use for the treatment of AD and other age-related diseases

Therapeutic potential of MEK inhibition in acute myelogenous leukemia: rationale for "vertical" and "lateral" combination strategies

: In hematological malignancies, constitutive activation of the RAF/MEK/ERK pathway is frequently observed, conveys a poor prognosis, and constitutes a promising target for therapeutic intervention. Here, we investigated the molecular and functional effects of pharmacological MEK inhibition in cell line models of acute myeloid leukemia (AML) and freshly isolated primary AML samples. The small-molecule, ATP-non-competitive, MEK inhibitor PD0325901 markedly inhibited ERK phosphorylation and growth of several AML cell lines and approximately 70 % of primary AML samples. Growth inhibition was due to G(1)-phase arrest and induction of apoptosis. Transformation by constitutively active upstream pathway elements (HRAS, RAF-1, and MEK) rendered FDC-P1 cells exquisitely prone to PD0325901-induced apoptosis. Gene and protein expression profiling revealed a selective effect of PD0325901 on ERK phosphorylation and compensatory upregulation of the RAF/MEK and AKT/p70( S6K ) kinase modules, potentially mediating resistance to drug-induced growth inhibition. Consequently, in appropriate cellular contexts, both "vertical" (i.e., inhibition of RAF and MEK along the MAPK pathway) and "lateral" (i.e., simultaneous inhibition of the MEK/ERK and mTOR pathways) combination strategies may result in synergistic anti-leukemic effects. Overall, MEK inhibition exerts potent growth inhibitory and proapoptotic activity in preclinical models of AML, particularly in combination with other pathway inhibitors. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective targeted strategies for the treatment of AML

Controlled Coprecipitation of Amorphous Cerium-Based Carbonates with Suitable Morphology as Precursors of Ceramic Electrolytes for IT-SOFCs

To be suitable as electrolytes in intermediate temperature solid oxide fuel cell (IT-SOFC), ceramic precursors have to be characterized by high sintering aptitude for producing fully densified products which are needed for this kind of application. Therefore, synthesis processes able to prepare highly reactive powders with low costs are noteworthy to be highlighted. It has been shown that amorphous coprecipitates based on cerium doped (and codoped) hydrated hydroxycarbonates can lead to synthesized ceramics with such desired characteristics. These materials can be prepared by adopting a simple coprecipitation technique using ammonium carbonate as precipitating agent. As a function of both the molar ratio between carbonate anions and total metallic cations, and the adopted mixing speed, the coprecipitate can be either amorphous, owning a very good morphology, or crystalline, owning worse morphology, packing aptitude, and sinterability. The amorphous powders, upon a mild calcination step, gave rise to the formation of stable solid solutions of fluorite-structured ceria maintaining the same morphology of the starting powders. Such calcined powders are excellent precursors for sintering ceramic electrolytes at low temperatures and with very high electrical conductivity in the intermediate temperature range (i.e., 500⁻700 °C). Therefore, irrespective of the actual composition of ceria-based systems, by providing an accurate control of both chemical conditions and physical parameters, the coprecipitation in the presence of ammonium carbonate can be considered as one of the most promising synthesis route in terms of cost/effectiveness to prepare excellent ceramic precursors for the next generation of IT-SOFC solid electrolytes

Prognostic value of rhodamine-efflux and MDR-1/p-170 expression in childhood acute leukemia

The evidence that mechanisms other than P-170 expression may influence its ''pump'' and the retention/efflux of chemotherapeutic agents, prompted us to investigate the value of a functional multidrug resistance (MDR) assay in a series of childhood acute leukemia samples. Forty acute leukemia cases, mainly of lymphoid origin (ALL), were evaluated for MDR expression using a functional test based on rhodamine-123 efflux (Rhd-E). This was correlated with the quantification of P-170 external epitopes based on the positivity with the 4E3.16 and MRK16 monoclonal antibodies (MAbs). When compared with the status of the disease and response to treatment, the mean (m) Rhd-E value was significantly lower in patients at diagnosis (m=7.1% versus m=22.4% at relapse) and in patients who achieved a complete remission (m=8.81% versus 31.5% in resistant cases). In the 22 samples analyzed, an overall correlation was found between the functional assay and the P-170 expression (r=0.6), despite the much lower level of MDR positivity recognized by the immunocytometric method (m=0.78% and 0.9% in cases at diagnosis versus m=3.7% and 4.1% at relapse, with the 4E3.16 and MRK16 MoAbs). These data suggest that the assessment of the clinical impact of MDR expression in pediatric ALL should be based on methodological approaches capable of providing information extended to the P-170 pump function, rather then only on its gene and protein expression

Does smoking increase risk for caries? A cross-sectional study in an Italian Military Academy

Background/Aims: Traditionally, tobacco is considered as part of the military culture. A cross-sectional survey was designed to clarify if smoking habit increases the caries risk in a sample of Italian adults attending a Military Academy. Methods: Clinical examinations including dental caries and presence of bleeding at probing were carried out following WHO criteria. Related socio-behavioural factors were collected. Four calibrated examiners observed 763 subjects (men = 722; 94.6% and women = 41; 5.4%). Results: One of the 763 subjects did not declare the smoking status and was excluded from the analysis. Hundred twenty-six (16.5%) subjects claimed to have never smoked, 200 (26.3%) were coded as light smokers and 436 (57.2%) as heavy tobacco users. Statistically significant linear trend across the educational level (p = 0.03), self-satisfaction with the appearance of teeth and gums (p = 0.04) and dental check-up in the past 6 months (p = 0.02) was found among the 3 subgroups. Almost the entire sample showed caries experience (84.1%). Mean DS ranged from 0.6 in the nonsmokers subgroup to 1.1 in the heavy smokers. Differences among means were statistically significant for DS, DMFS and Significant Caries Index (p = 0.01, 0.04 and 0.03, respectively). The zero-inflated regression model showed that caries severity was significantly associated with smoking habit (p = 0.02), dental check-up in the past 6 months (p = 0.01), self-satisfaction with the appearance of teeth and gums (p < 0.01) and healthy gums (p = 0.04). Conclusion: Heavy smokers attending a Military Academy showed a higher prevalence of caries, confirming a correlation between the disease and tobacco use

Eye Tracking Glasses in Higher Education Classrooms: First Findings from an International Project for Improving Teaching

The paper describes the purpose, the methods, and the results of the project “Teaching in Higher Education Effectively via Eye-tracking (THEE)”, funded by the Erasmus Plus Programme (KA2 - Cooperation for Innovation and the Exchange of Good Practices KA203 - Strategic Partnerships for Higher Education). The project studied the eye movements of higher education teachers and students to reflect on how to improve the teaching-learning process. The participants were 4 professors and 12 students who wore eye tracking glasses during the lessons. The results of the study demonstrate a clear benefit of the approach based on collecting eye tracking data and teachers’ self-reflection on their own classroom practice. The purpose of the project is to realise an online course in four languages to contribute to the university teachers’ training