The chemical composition of the essential oils of Laurus nobilis, Juniperus oxycedrus ssp. oxycedrus, Thuja orientalis, Cupressus sempervirens ssp. pyramidalis, Pistacia palaestina, Salvia officinalis, and Satureja thymbra was determined by GC/MS analysis. Essential oils have been evaluated for their inhibitory activity against SARS-CoV and HSV-1 replication in vitro by visually scoring of the virus-induced cytopathogenic effect post-infection. L. nobilis oil exerted an interesting activity against SARS-CoV with an IC(50) value of 120 microg/ml and a selectivity index (SI) of 4.16. This oil was characterized by the presence of beta-ocimene, 1,8-cineole, alpha-pinene, and beta-pinene as the main constituents. J. oxycedrus ssp. oxycedrus oil, in which alpha-pinene and beta-myrcene were the major constituents, revealed antiviral activity against HSV-1 with an IC(50) value of 200 microg/ml and a SI of 5.

We studied the effects of rapamycin on cultures of erythroid progenitors derived from the peripheral blood of 10 beta-thalassaemia patients differing widely with respect to their potential to produce foetal haemoglobin (HbF). For this, we employed the two-phase liquid culture procedure for growing erythroid progenitors, high performance liquid chromatography for analysis of HbF production and reverse transcription polymerase chain reaction for quantification of the accumulation of globin mRNAs. The results demonstrated that rapamycin induced an increase of HbF in cultures from all the beta-thalassaemia patients studied and an increase of their overall Hb content/cell. The inducing effect of rapamycin was restricted to gamma-globin mRNA accumulation, being only minor for beta-globin and none for alpha-globin mRNAs. The ability of rapamycin to preferentially increase gamma-globin mRNA content and production of HbF in erythroid precursor cells from beta-thalassaemia patients is of great importance as this agent (also known as sirolimus or rapamune) is already in clinical use as an anti-rejection agent following kidney transplantation. These data suggest that rapamycin warrants further evaluation as a potential therapeutic drug in beta-thalassaemia and sickle cell anaemia.

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Peptide nucleic acids (PNAs) are DNA-mimicking molecules in which the sugar-phosphate backbone is replaced by a pseudopeptide backbone composed of N-(2-aminoethyl)glycine units. We determined whether double-stranded molecules based on PNAs and PNA-DNA-PNA (PDP) chimeras could be capable of stable interactions with nuclear proteins belonging to the Sp1 transcription factor family and, therefore, could act as decoy reagents able to inhibit molecular interactions between Sp1 and DNA. Since the structure of PNA/PNA hybrids is very different from that of the DNA/DNA double helix, they could theoretically alter the molecular structure of the double-stranded PNA-DNA-PNA chimeras, perturbing interactions with specific transcription factors. We found that PNA-based hybrids do not inhibit Sp1/DNA interactions. In contrast, hybrid molecules based on PNA-DNA-PNA chimeras are very effective decoy molecules, encouraging further experiments focused on the possible use of these molecules for the development of potential agents for a decoy approach in gene therapy. In this respect, the finding that PDPbased decoy molecules are more resistant than DNA/ DNA hybrids to enzymatic degradation appears to be of great interest. Furthermore, their resistance can even be improved after complexation with cationic liposomes to which PDP/PDP chimeras are able to bind by virtue of their internal DNA structure.In vitro transfection of cis elements that decoy against nuclear factors leads to alteration of gene expression and was recently proposed in molecular medicine as a novel tool for the possible therapy of several disorders (1-12). One of the most effective decoy approaches so far described involves nuclear proteins belonging to the NF-B 1 superfamily (7-9, 13-20).Decoy molecules against NF-B inhibit the expression of NF-B regulated genes (MHC complex genes, IL2 receptor ␣, Igk, IL6, ␦ opioid receptor, preprogalanin, adhesion molecule-1) (20). More recently, dumbell DNA decoy elements against NF-B were demonstrated to be active in inhibiting ex vivo transcription driven by the long terminal repeat (LTR) of human immunodeficiency type-1 virus (HIV-1) (19). In addition to proteins belonging to the NF-B superfamily, decoy molecules for other target transcription factors, such as HNF-1, RFX1, nuclear factor YB, E2F, cAMP-response element, and Sp1, were found to be effective (1-6, 10 -12, 21).As to the molecular targets for the decoy approach, proteins belonging to the Sp1 family are of great interest since these transcription factors are involved in the regulation of the expression of several genes relevant to human pathologies, including those encoding vascular endothelial growth factor, plasminogen-activator inhibitor type-1 (PAI-1), COL1A2, urokinase-type plasminogen activator (uPA), and uPA receptor (3,(21)(22)(23)(24)(25). Sp1 binding sites are also present in the HIV-1 LTR (26). Thus, the development of experimental approaches based on Sp1 decoys to modulate the transcription of Sp1-dependent genes appears to be of great interest (3).Rec...