Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats.

Several studies indicate that adult stem cells may improve the recovery from acute tissue injury. It has been suggested that they may contribute to tissue regeneration by the release of paracrine factors promoting proliferation of tissue resident cells. However, the factors involved remain unknown. In the present study we found that microvesicles (MVs) derived from human liver stem cells (HLSC) induced in vitro proliferation and apoptosis resistance of human and rat hepatocytes. These effects required internalization of MVs in the hepatocytes by an alpha(4)-integrin-dependent mechanism. However, MVs pre-treated with RNase, even if internalized, were unable to induce hepatocyte proliferation and apoptosis resistance, suggesting an RNA-dependent effect. Microarray analysis and quantitative RT-PCR demonstrated that MVs were shuttling a specific subset of cellular mRNA, such as mRNA associated in the control of transcription, translation, proliferation and apoptosis. When administered in vivo, MVs accelerated the morphological and functional recovery of liver in a model of 70% hepatectomy in rats. This effect was associated with increase in hepatocyte proliferation and was abolished by RNase pre-treatment of MVs. Using human AGO2, as a reporter gene present in MVs, we found the expression of human AGO2 mRNA and protein in the liver of hepatectomized rats treated with MVs. These data suggested a translation of the MV shuttled mRNA into hepatocytes of treated rats. In conclusion, these results suggest that MVs derived from HLSC may activate a proliferative program in remnant hepatocytes after hepatectomy by a horizontal transfer of specific mRNA subsets.

Use of agricultural by-products in the development of an agro-energy chain: A case study from the Umbria region.

Use of agricultural and livestock by-products for anaerobic digestion (AD), in total or partial substitution of the maize silage was evaluated from an environmental and economical point of view. The evaluation process included three methodological interdependent and consequential steps: the chemical stage at laboratory and plant level, the environmental and economic steps developing the Life Cycle Assessment and Life Cycle Costing jointly. The laboratory test showed that the two mixtures prepared with by-products, in partial (MIX A) and total (MIX B) substitution of maize silage, did not show differences in bio-methane production compared to a reference mixture with the 33% of maize silage. All mixtures tested at full-scale plant, showed the same performances, resulting in a similar energy production. Environmentally, MIX B increased greenhouse gas credits derived from the avoided production of mineral fertiliser for the energetic crops, resulting also in better economic performances. The break-even transport distances follow the positive environmental pattern result, in contrast to what was found for the break-even transport distances from the economic point of view.

Change in gene expression profile induced by alpha-melanocyte stimulating hormone in a malignant mesothelioma cell line.

We have previously reported that the peptide a-melanocyte stimulating hormone (alpha-MSH) has antiproliferative effects in human malignant mesothelioma cells. To determine the molecular mechanisms underlying such effects, we investigated the changes in gene expression profile induced by the alpha-MSH analog [Nle4 -DPhe7 ]-alpha-MSH (NDP-alpha-MSH) in a human malignant mesothelioma cell line. The cDNA macroarray technique revealed changes in expression of genes involved in cell growth, adhesion, signal transduction, and transcription. In particular, NDP-alpha-MSH down-regulated expression of B-Myb and Myc, two oncogenes considered of paramount importance for cell proliferation and cancer. Further, NDP-alpha-MSH exerted a favorable transcriptional regulation of certain integrins and their signaling pathways. Finally, peptide treatment was associated with a prominent inhibition of IL-13, a cytokine with tumor-promoting effects. The data indicate that the influences of alpha-MSH extend beyond the established anti-inflammatory effects in normal cells to include cell cycle regulatory properties in malignant cells.

Antimicrobial properties of alpha-MSH and related synthetic melanocortins.

The natural antimicrobial peptides are ancient host defense effector molecules, present in organisms across the evolutionary spectrum. Several properties of alpha-melanocyte stimulating hormone (alpha-MSH) suggested that it could be a natural antimicrobial peptide. Alpha-MSH is a primordial peptide that appeared during the Paleozoic era, long before adaptive immunity developed and, like natural antimicrobial molecules, is produced by barrier epithelia, immunocytes, and within the central nervous system. alpha-MSH was discovered to have antimicrobial activity against two representative pathogens, Staphylococcus aureus and Candida albicans. The candidacidal influences of alpha-MSH appeared to be mediated by increases in cell cyclic adenosine monophosphate (cAMP). The cAMP-inducing capacity of alpha-MSH likely interferes with the yeast's own regulatory mechanisms of this essential signaling pathway. It is remarkable that this mechanism of action in yeast mimics the influences of alpha-MSH in mammalian cells in which the peptide binds to G-protein-linked melanocortin receptors, activates adenylyl cyclase, and increases cAMP. When considering that most of the natural antimicrobial peptides enhance the local inflammatory reaction, the anti-inflammatory and antipyretic effects of alpha-MSH confer unique properties to this molecule relative to other natural antimicrobial molecules. Synthetic derivatives, chemically stable and resistant to enzymatic degradation, could form the basis for novel therapies that combine anti-inflammatory and antimicrobial properties.