Hepcidin levels and their determinants in different types of myelodysplastic syndromes

Iron overload may represent an additional clinical problem in patients with Myelodysplastic Syndromes (MDS), with recent data suggesting prognostic implications. Beyond red blood cells transfusions, dysregulation of hepcidin, the key iron hormone, may play a role, but studies until now have been hampered by technical problems. Using a recently validated assay, we measured serum hepcidin in 113 patients with different MDS subtypes. Mean hepcidin levels were consistently heterogeneous across different MDS subtypes, with the lowest levels in refractory anemia with ringed sideroblasts (RARS, 1.43 nM) and the highest in refractory anemia with excess blasts (RAEB, 11.3 nM) or in chronic myelomonocytic leukemia (CMML, 10.04 nM) (P = 0.003 by ANOVA). MDS subtypes remained significant predictors of hepcidin in multivariate analyses adjusted for ferritin and transfusion history. Consistently with current knowledge on hepcidin action/regulation, RARS patients had the highest levels of toxic non-transferrin-bound-iron, while RAEB and CMML patients had substantial elevation of C-Reactive Protein as compared to other MDS subtypes, and showed lost of homeostatic regulation by iron. Growth differentiation factor 15 did not appear as a primary hepcidin regulator in this series. If confirmed, these results may help to calibrate future treatments with chelating agents and/or hepcidin modulators in MDS patients.     

Reproducibility and Respiratory Function Correlates of Exhaled Breath Fingerprint in Chronic Obstructive Pulmonary Disease

Background

The electronic nose (e nose) provides distinctive breath fingerprints for selected respiratory diseases. Both reproducibility and respiratory function correlates of breath fingerprint are poorly known.

Objectives

To measure reproducibility of breath fingerprints and to assess their correlates among respiratory function indexes in elderly healthy and COPD subjects.

Method

25 subjects (5 COPD patients for each GOLD stage and 5 healthy controls) over 65 years underwent e-nose study through a seven sensor system and respiratory function tests at times 0, 7, and 15 days. Reproducibility of the e nose pattern was computed. The correlation between volatile organic compound (VOC) pattern and respiratory function/clinical parameters was assessed by the Spearman''s rho.

Measurements and Main Results

VOC patterns were highly reproducible within healthy and GOLD 4 COPD subjects, less among GOLD 1–3 patients.VOC patterns significantly correlated with expiratory flows (Spearman''s rho ranging from 0.36 for MEF25% and sensor Co-Buti-TPP, to 0.81 for FEV1% and sensor Cu-Buti-TPP p<0.001)), but not with residual volume and total lung capacity.

Conclusions

VOC patterns strictly correlated with expiratory flows. Thus, e nose might conveniently be used to assess COPD severity and, likely, to study phenotypic variability. However, the suboptimal reproducibility within GOLD 1–3 patients should stimulate further research to identify more reproducible breath print patterns.     

Inhibition of stromal CXCR4 impairs development of lung metastases

Compelling evidence has emerged in recent years indicating that stromal cells play a critical role in disease progression. CXCR4 is a G-protein-coupled receptor with a major role in lymphocyte homing. Its ligand, CXCL12, is a highly efficient chemotactic factor for T cells, monocytes, pre-B cells, dendritic cells and myeloid bone marrow-derived cells (BMDCs). In addition, the CXCR4-CXCL12 axis plays a central role in tumor growth and metastasis. To evaluate the effect of genetic CXCR4 reduction on metastasis development, murine melanoma B16 cells were injected into the tail vein of C57BL/6 CXCR4(+/+) and CXCR4(+/-) mice in the presence of the CXCR4 inhibitor, Plerixafor (previously named AMD3100). Although lung metastases developed in wild-type CXCR4(+/+) and heterozygote CXCR4(+/-) mice, nodules were significantly smaller in the latter. CXCR4 pharmacological inhibition by Plerixafor further reduced lung metastases in CXCR4(+/-) mice, preserving the pulmonary architecture (4.18?±?1.38?mm(2) vs. 1.11?±?0.60?mm(2), p?=?0.038). A reduction in LY6G-positive myeloid/granulocytic cells and in p38 MAPK activation was detected in lungs from CXCR4(+/-) mice compared to CXCR4(+/+) mice [LY6G-positive myeloid CXCR4(+/-) vs. CXCR4(+/+) (p?=?0.0004); CXCR4(+/+) vs. CXCR4(+/+) Plerixafor-treated (p?=?0.0031)] suggesting that CXCR4 reduction on myeloid-derived cells reduced their recruitment to the lung, consequently impairing lung metastases. Our findings argue in favor of a specific role of CXCR4 expressed in stromal cells that condition the pro-tumor microenvironment. In this scenario, CXCR4 antagonists will target neoplastic cells as well as the pro-tumor stromal microenvironment.     

Effect of nutrients on decomposition of Ruppia cirrhosa in a shallow coastal lagoon

Hydrobiologia - Here we study the pattern of disappearance of Ruppia cirrhosa Petagna (Grande) litter in the field and evaluate several variables that determine the loss rate: external nitrogen and...     

Effects of tellurite on growth of Saccharomyces cerevisiae

The effects of potassium tellurite on growth and survival of rho⁺ and rho⁰ Saccharomyces cerevisiae strains were investigated. Both rho⁺ and rho⁰ strains grew on a fermentable carbon source with up to 1.2 mM K₂TeO₃, while rho⁺ yeast cells grown on a non-fermentable carbon source were inhibited at tellurite levels as low as 50 μM suggesting that this metalloid specifically inhibited mitochondrial functions. Growth of rho⁺ yeast cells in the presence of increasing amount of tellurite resulted in dose-dependent blackening of the culture, a phenomenon not observed with rho⁰ cultures. Transmission electron microscopy of S. cerevisiae rho⁺ cells grown in the presence of tellurite showed that blackening was likely due to elemental tellurium (Te⁰) that formed large deposits along the cell wall and small precipitates in both the cytoplasm and mitochondria.     

New insights into the operative network of FaEO,an enone oxidoreductase from <Emphasis Type="Italic">Fragaria x ananassa</Emphasis> Duch.

The 2-methylene-furan-3-one reductase or Fragaria x ananassa Enone Oxidoreductase (FaEO) catalyses the last reductive step in the biosynthesis of 4-hydroxy-2,5-dimethyl-3(2H)-furanone, a major component in the characteristic flavour of strawberries. In the present work, we describe the association between FaEO and the vacuolar membrane of strawberry fruits. Even if FaEO lacks epitopes for stable or transient membrane-interactions, it contains a calmodulin-binding region, suggesting that in vivo FaEO may be associated with the membrane via a peripheral protein complex with calmodulin. Moreover, we also found that FaEO occurs in dimeric form in vivo and, as frequently observed for calmodulin-regulated proteins, it may be expressed in different isoforms by alternative gene splicing. Further mass spectrometry analysis confirmed that the isolated FaEO consists in the already known isoform and that it is the most characteristic during ripening. Finally, a characterization by absorption spectroscopy showed that FaEO has specific flavoprotein features. The relevance of these findings and their possible physiological implications are discussed.     

Hyper-expression of small nucleolar RNAs (snoRNAs) in female inflorescences of hazelnut (Corylus avellana L.) supports rRNA aggregation in vitro

Under certain in vitro (salt and temperature) conditions rRNA aggregation occurs in female inflorescences but not in leaves or pollen RNA preparations from hazelnut (Corylus avellana L.), a species of economic interest. This paper describes experiments addressing an explanation of this phenomenon. The experiments demonstrate that: (i) trans-acting factors induce rRNA aggregate formation in female inflorescences RNA preparations; (ii) these factors support aggregation also of heterologous rRNA; (iii) aggregation is a function of temperature pre-treatment of rRNA and not of source 18S rRNA; (iv) the factors inducing rRNA aggregates are sensitive to RNase; (v) antisense small nucleolar RNAs (snoRNAs) participate in rRNA aggregate formation. snoRNAs are involved in pre-rRNA spacer cleavages, and are required for the two most common types of rRNA modifications: 2'-O-ribose methylation and pseudouridylation. Even though it is questionable whether rRNA aggregation really happens in female inflorescence in vivo, the phenomenon observed in vitro may reflect the abundance of snoRNAs in these reproductive structures. In fact the level of accumulation of three tested snoRNAs, R1, U14 and U3, is much higher in female inflorescence than in leaves or pollen of hazelnut. This finding opens the possibility of studying the role of snoRNAs in tissue development in plants.