139 research outputs found
miRNA 34a, 100, and 137 modulate differentiation of mouse embryonic stem cells
No full textMicroRNAs (miRNAs) play an important
role in proper function and differentiation of mouse
embryonic stem cells (ESCs). We performed a systematic
comparison of miRNA expression in undifferentiated
vs. differentiating ESCs. We report that 138 miRNAs
are increased on the induction of differentiation. We
compared the entire list of candidate mRNA targets
of up-regulated miRNAs with that of mRNA downregulated
in ESCs on induction of differentiation.
Among the candidate targets emerging from this analysis,
we found three genes, Smarca5, Jarid1b, and Sirt1,
previously demonstrated to be involved in sustaining
the undifferentiated phenotype in ESCs. On this basis,
we first demonstrated that Smarca5 is a direct target of
miR-100, Jarid1b of miR-137, and we also confirmed
previously published data demonstrating that Sirt1 is a
direct target of miR-34a in a different context. The
suppression of these three miRNAs by anti-miRs caused
the block of ESC differentiation induced by LIF withdrawal.
On the other hand, the overexpression of the
three miRNAs resulted in an altered expression of
differentiation markers. These results demonstrate that
miR-34a, miR-100, and miR-137 are required for
proper differentiation of mouse ESCs, and that they
function in part by targeting Sirt1, Smarca5, and
Jarid1b mRNAs.—Tarantino, C., Paolella, G., Cozzuto,
L., Minopoli, G., Pastore, L., Parisi, S., Russo, T.
miRNA 34a, 100, and 137 modulate differentiation of
mouse embryonic stem cells
Geochemistry of melt inclusions from the Fondo Riccio and Minopoli 1 eruptions at Campi Flegrei (Italy)
No full textCampi Flegrei is a large volcanic complex (similar to 150 km(2)) located west of the city of Naples, Italy. The area has been the site of volcanic activity for more than 60,000 years and represents a potential volcanic hazard owing to the large local population. In this study, the geochemistry of the magma associated with two different eruptions at Campi Flegrei has been characterized, with the aim to identify geochemical trends that may help to predict the style and nature of future eruptions. Two eruptions of different age and eruptive style have been selected for study, Fondo Riccio (9.5 ka) and Minopoli 1 (11.1 ka). A scoria (CF-FR-C1) and a bomb (CF-FR-C2) were collected from the Fondo Riccio eruption, and two scoria samples were collected from the Minopoli 1 (CF-Mil-C1 and C2) eruptive products.
The pre-eruptive volatile content of magma plays an important role in the style of eruption. The original volatile content of magma can be assessed from studies of melt inclusion (MI) contained in phenocrysts. MI data show two trends for Fondo Riccio - one from latite to trachyte for MI in Fe-rich diopside (C1) and another from trachybasalt to shoshonite for MI in Mg-rich diopside (C2) and for MI in olivine (C1). Minopoli 1 MI data show two different compositions - basaltic for MI in clinopyroxene (MiI-C1) and trachybasalt for MI in olivine (MiI-C1) and clinopyroxene (MiI-C2). Major and trace element data for Fondo Riccio MI show a compositional gap between Mg# 78 and 83, whereas Minopoli 1 MI have Mg# between 85 and 89 and show no compositional gap. Clinopyroxene compositions fall in the diopside-salite field for Fondo Riccio and in the diopside field for Minopoli 1. Fondo Riccio olivine compositions show a wider range (Fo(84.60) to Fo(86.77)), compared to Minopoli 1 olivine (Fo(77) to Fo(78.5)). Analyses of reheated MI suggest trends in MI volatile contents that correlate with SiO2 concentration. In particular, more evolved MI show higher Cl and lower S compared to less evolved MI. The H2O content of MI from the two eruptions overlap but suggest that the Fondo Riccio magma may have been more water-rich. The higher H2O content of the Fondo Riccio magma (2.5 to 6.9 wt.%) compared to Minopoli 1 (1-3.5 wt.%) is consistent with the more explosive nature of Fondo Riccio eruption compared to Minopoli 1
Volcanic CO2 detection with a DFM/OPA-based lidar
No full textThe DFM/OPA-based lidar BILLI was used to investigate the volcanic plume released by the hydrothermal vent of Pisciarelli, in the Campi Flegrei volcano. BILLI remotely measured CO2 concentrations in cross-sections of the nearvent plume using the differential absorption technique. To our knowledge, this is the first example of lidar-based measurement of volcanic CO2 . The spatial resolution was 1.5 m and the temporal resolution 20 s. © 2015 Optical Society of America
A reliable analytical procedure to determine the carbon isotopic signature of CO2-bearing COH fluids generated in petrological experiments
No full textThe ratio of stable carbon isotopes, δ13C, serves as a fundamental tracer for geological processes.
Experiments aiming to replicate isotopic exchange between carbon reservoirs encounter significant analytical
challenges due to the limited sample size and issues related to sampling, particularly when dealing with volatile
species. Here we present a novel methodology that integrates a capsule-piercing device, a quadrupole mass spec-
trometer (QMS), and isotopic ratio mass spectrometry (IRMS) to measure the CO2 concentration and natural-like
δ13C ratio of CO2 in the volatile COH phase generated in petrological experiments. To validate the technique,
we first analyze the COH fluid resulting from the thermal decomposition of 1 mg of anhydrous oxalic acid. The
optimal values of the carrier gas flow in the QMS, sampling times, and chromatography column temperature for
IRMS are determined. The high degree of similarity, within acceptable errors, observed in both compositional
and isotopic analyses indicates a robust reproducibility, minimally affected by contamination and fractiona-
tion effects during sampling. We also show that this methodology can be applied for estimating the δ13C of
CO2 produced from high-pressure, high-temperature, redox-buffered piston–cylinder experiments. This offers a
multitude of opportunities in designing experiments focused on determining isotopic fractionation models for
geological processes that involve, but are not restricted to, CO2-bearing COH fluids
New ground-based lidar enables volcanic CO2 flux measurements
No full textThere have been substantial advances in the ability to monitor the activity of hazardous volcanoes in recent decades. However, obtaining early warning of eruptions remains challenging, because the patterns and consequences of volcanic unrests are both complex and nonlinear. Measuring volcanic gases has long been a key aspect of volcano monitoring since these mobile fluids should reach the surface long before the magma. There has been considerable progress in methods for remote and in-situ gas sensing, but measuring the flux of volcanic CO2-the most reliable gas precursor to an eruption-has remained a challenge. Here we report on the first direct quantitative measurements of the volcanic CO2 flux using a newly designed differential absorption lidar (DIAL), which were performed at the restless Campi Flegrei volcano. We show that DIAL makes it possible to remotely obtain volcanic CO2 flux time series with a high temporal resolution (tens of minutes) and accuracy (<30%). The ability of this lidar to remotely sense volcanic CO2 represents a major step forward in volcano monitoring, and will contribute improved volcanic CO2 flux inventories. Our results also demonstrate the unusually strong degassing behavior of Campi Flegrei fumaroles in the current ongoing state of unrest
DIMETHYLFUMARATE MEDIATES CERVICAL CARCINOMA FERROPTOSIS THROUGH REDOX-RELATED PATHWAYS
No full textCervical cancer (CC) represents the fourth leading cause of women death worldwide. Development of CC is based on papillomavirus (HPV) persistent infections which boosts multistep transformation. CC has a high recurrence rate, and it is a relatively drugresistant disease, indeed acquired resistance to cisplatin is frequently observed. Therefore, there is a need to identify novel drugs against CC. Dimethylfumarate (DMF) is a clinically approved treatment for psoriasis/multiple sclerosis and emerging studies also indicate DMF antitumor activity in some cancers [1]. DMF action involves both Nrf2dependent and independent pathways.
We demonstrate that DMF has an antiproliferative effect in SiHa cells. In particular, we were interested in ferroptosis, a novel form of cell death mediated by iron dependent lipid peroxidation. We compared DMF effectiveness with different wellknown inducers of ferroptosis by using cell viability and colony assays. Malondialdehyde and lipid peroxidation assays demonstrated that in SiHa cells, DMF induces ferroptoticlike cell death. Furthermore, we analyzed the expression of a group of ferroptosisrelated genes. The results showed that mRNA levels of SAT1 (Spermidine/Spermine N1Acetyltransferase 1) and PTGS2 (Prostaglandin endoperoxide synthase2), two well know markers of ferroptosis, were strongly increased upon DMF treatments. Since some studies reported that STAT3 and NRF2 are hyperactivated in tumors, and their interaction can regulate tumor progression, we focused on these pathways. Molecular analyses demonstrated that DMF can intercept both: it stimulates protective Nrf2 activity but also inactivates STAT3 that could finally sensitize these cells to ferroptosis.
Our data albeit in its infancy, suggest therapeutic potentials of DMF for CC treatment and repurpose DMFmediated strategies involving Nrf2STAT3 cross talk as a promising option
Effects of S–adenosyl–L–methionine on the invasion and migration of head and neck squamous cancer cells and analysis of the underlying mechanisms
No full textS-Adenosyl-L-methionine (AdoMet) is the principal methyl donor in transmethylation reactions fundamental to sustaining epigenetic modifications. Over the past decade, AdoMet has been extensively investigated for its anti-proliferative, pro-apoptotic and anti-metastatic roles in several types of human cancer. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide, and is an aggressive type of cancer that is associated with a high recurrence rate, metastasis and poor treatment outcomes. The present study demonstrates, for the first time, to the best of our knowledge, that AdoMet induces cell cycle arrest and inhibits the migratory and invasive ability of two different HNSCC cell lines, oral Cal-33 and laryngeal JHU-SCC-011 cells. In both cell lines, AdoMet attenuated cell cycle progression, decreased the protein level of several cyclins and downregulated the expression of p21 cell cycle inhibitor. Moreover, AdoMet was able to inhibit Cal-33 and JHU-SCC-011 cell migration in a dose-dependent manner after 24 and 48 h, respectively, and also induced a significant reduction in the cell invasive ability, as demonstrated by Matrigel invasion assay monitored by the xCELLigence RTCA system. Western blot analysis of several migration and invasion markers confirmed the inhibitory effects exerted by AdoMet on these processes and highlighted AKT, β-catenin and small mothers against decapentaplegic (SMAD) as the main signaling pathways modulated by AdoMet. The present study also demonstrated that the combination of AdoMet and cisplatin synergistically inhibited HNSCC cell migration. Taken together, these findings demonstrate that the physiological compound, AdoMet, affects the motility and extracellular matrix invasive capability in HNSCC. Thus, AdoMet may prove to be a good candidate for future drug development against metastatic cancer
Mandibular nerve regenerating through venous graft as guide. Experimental study in rabbit.
No full textRedox modulation and induction of ferroptosis by dimethyl fumarate in cervical carcinoma
No full textCervical cancer (CC) is the fourth most common cause of women death. The papillomavirus (HPV) persistent infection is the lead- ing cause for the development of CC that progresses through multistep transformation. Drug resistance and relapse are fre- quently observed in CC after conventional chemotherapy and radiotherapy. Therefore, there is a need to find new drugs against CC. Dimethyl fumarate (DMF) is an FDA-approved anti-inflam- matory drug and emerging studies suggest that DMF also exert an anti-tumor activity in some cancers. We were interested to fer- roptosis, a type of cell death caused by iron-dependent lipid per- oxidation. Using cell viability and colony assay, we tested the effectiveness of DMF alone in comparison to other well-known inducers of ferroptosis in SiHa and C4I cells. We performed fer- roptosis related-genes expression analysis, lipid peroxidation and malondialdehyde assays demonstrating that DMF induces ferrop- tosis in a concentration-dependent manner in both cell lines. Next, we investigated if the combination of DMF with sub-cyto- toxic ferroptotic-drugs was able to ameliorate ferroptosis. We found that co-treatments of DMF/sulfasalazine (SAS) were asso- ciated with enhanced cell death. To elucidate molecular mecha- nisms underlying these effects we analyzed the NRF2 antioxidant pathway. Real-time PCR and western blot assays showed an induction of NRF2 protein and NRF2-dependent genes, such as SLC7A11 involved in GSH synthesis. In contrast with the observed SLC7A11 increase, we detected a strong reduction of glutathione (GSH) under DMF/SAS treatments. These results indicate that SAS cooperates in GSH depletion favoring ferrop- tosis. Since DMF has been found to influence NF-kB, STAT3 signaling we also tested IL-6 levels, a NF-kB target, and phos- phorylation of STAT3 in DMF/SAS treatments. Our results demonstrate that both these pathways are reduced in presence of SAS, implicating that DMF/SAS exhibited a strong killing-effect than either DMF or SAS alone
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