Deciphering the molecular machinery of stem cells: a look at the neoblast gene expression profile

Comparison of the gene-expression profiles of planarians in which all adult pluripotent stem cells (neoblasts) were eliminated and wild-type worms identified a putative neoblast-restricted gene set. This included many genes involved in chromatin modeling and RNA metabolism, suggesting that epigenetic modifications and post-transcriptional regulation are important for neoblast regulation

Cell-specific pattern of berberine pleiotropic effects on different human cell lines

The natural alkaloid berberine has several pharmacological properties and recently received attention as a potential anticancer agent. In this work, we investigated the molecular mechanisms underlying the anti-Tumor effect of berberine on glioblastoma U343 and pancreatic carcinoma MIA PaCa-2 cells. Human dermal fibroblasts (HDF) were used as non-cancer cells. We show that berberine differentially affects cell viability, displaying a higher cytotoxicity on the two cancer cell lines than on HDF. Berberine also affects cell cycle progression, senescence, caspase-3 activity, autophagy and migration in a cell-specific manner. In particular, in HDF it induces cell cycle arrest in G2 and senescence, but not autophagy; in the U343 cells, berberine leads to cell cycle arrest in G2 and induces both senescence and autophagy; in MIA PaCa-2 cells, the alkaloid induces arrest in G1, senescence, autophagy, it increases caspase-3 activity and impairs migration/invasion. As demonstrated by decreased citrate synthase activity, the three cell lines show mitochondrial dysfunction following berberine exposure. Finally, we observed that berberine modulates the expression profile of genes involved in different pathways of tumorigenesis in a cell line-specific manner. These findings have valuable implications for understanding the complex functional interactions between berberine and specific cell types

Protopine/Gemcitabine Combination Induces Cytotoxic or Cytoprotective Effects in Cell Type-Specific and Dose-Dependent Manner on Human Cancer and Normal Cells

The natural alkaloid protopine (PRO) exhibits pharmacological properties including anticancer activity. We investigated the effects of PRO, alone and in combination with the chemotherapeutic gemcitabine (GEM), on human tumor cell lines and non-tumor human dermal fibroblasts (HDFs). We found that treatments with different PRO/GEM combinations were cytotoxic or cytoprotective, depending on concentration and cell type. PRO/GEM decreased viability in pancreatic cancer MIA PaCa-2 and PANC-1 cells, while it rescued the GEM-induced viability decline in HDFs and in tumor MCF-7 cells. Moreover, PRO/GEM decreased G1, S and G2/M phases, concomitantly with an increase of subG1 phase in MIA PaCa-2 and PANC-1 cells. Differently, PRO/GEM restored the normal progression of the cell cycle, altered by GEM, and decreased cell death in HDFs. PRO alone increased mitochondrial reactive oxygen species (ROS) in MIA PaCa-2, PANC-1 cells and HDFs, while PRO/GEM increased both intracellular and mitochondrial ROS in the three cell lines. These results indicate that specific combinations of PRO/GEM may be used to induce cytotoxic effects in pancreatic tumor MIA PaCa-2 and PANC-1 cells, but have cytoprotective or no effects in HDFs

Effetti genotossici in Tricladi d'acqua dolce in seguito ad esposizione a solfato di cromo, un composto usato nell'attività conciaria

Genotoxic effects in freshwater Triclads after exposure to C riSO)3, chemical used in tanning processing. Freshwater Triclads, common invertebrates in unpolluted aquatic ecosystems, have been utilized as potential genotoxicity biomarkers. Some variations in the pattern of protein synthesis have been evidenced as a genomic response after exposure to toxic chemicals, in particular chromium sulphate, used in tanning processes. At the same time, in different samples, heat shock treatments were performed. Both treatments produced a drastic immediate decrease in the protein synthesis, observed by SDS-PAGE electrophoresis and fluorography. After 12 hours, fluorograms showed gradual restoring of protein synthesis followed by expression of specific polypeptides. As an example, the 41 kDa protein, synthesized in response to chromium sulphate, appeared to be specific and different from the two proteins (46 kDa and 55 kDa) detected after heat-shock treatments

Evolution of highly repeated DNA within the genus Triturus (Amphibia Urodela)

Highly repeated DNA is a main feature of urodele amphibian genomes. In Triturus this class of DNA consists of several sequence families differently arranged at both the molecular and the chromosomal level, showing varying degrees of conservation across species. Present data on highly repeated DNA in Triturus are here summarized and discussed with regard to the evolution and possible functional role of these sequences

A molecular cytogenetic comparison of planarians from the Dugesia gonocephala group (Platyhelminthes: Tricladida)

Planarians belonging to the Dugesia gonocephala group share extensive karyotype similarities when compared using classical cytological techniques. However, after in situ hybridization with rDNA, differences in localization and number of rDNA loci were identifiable among the species. Species-specific features in the rDNA structure have been observed by restriction pattern analysis. A family of long interspersed repeated elements (Del), isolated in Dugesia etrusca, and conserved only in some species of the group, was also informative in establishing specific genomic relationships among the species. We suggest that an understanding of the organization and evolution of repeated DNA sequences can be a useful tool for studying molecular mechanisms of evolutionary significance in planarians

A tandemly repeated DNA family originated from SINE-related elements in the European plethodontid salamanders (Amphibia, Urodela).

We have characterized a highly repetitive family, named Hy/Pol III, in the genome of the European salamanders Hydromantes (Plethodontidae). This family consists of short, tandemly repeated sequences organized in clusters, scattered through the genome as shown both by in situ hybridization to chromosomes and by Southern blot hybridization. The repeat unit is about 200 bp in length and it is a composite element since it contains a SINE-like retroposon with a tRNA structure, flanked by two short direct repeats. The whole element itself is bordered by two other direct repeats. The sequence data suggest that two elements, presumably derived from polymerase III transcripts, have been inserted one into the other, giving rise to the observed composite structure. During evolution the Hy/Pol III family was then amplified by tandem duplication at the DNA level. The inferred relationships between Hy/Pol III members from three representative species of the European Hydromantes suggests that a subfamily structure characterizes the evolutionary history of this family