Cyclin D1 is a major target of miR-206 in cell differentiation and transformation

miR-206, a member of the so-called myomiR family, is largely acknowledged as a specific, positive regulator of skeletal muscle differentiation. A growing body of evidence also suggests a tumor suppressor function for miR-206, as it is frequently downregulated in various types of cancers. In this study, we show that miR-206 directly targets cyclin D1 and contributes to the regulation of CCND1 gene expression in both myogenic and non-muscle, transformed cells. We demonstrate that miR-206, either exogenous or endogenous, reduces cyclin D1 levels and proliferation rate in C2C12 cells without promoting differentiation, and that miR-206 knockdown in terminally differentiated C2C12 cells leads to cyclin D1 accumulation in myotubes, indicating that miR-206 might be involved in the maintenance of the post-mitotic state. targeting of cyclin D1 might also account, at least in part, for the tumor-suppressor activity suggested for miR-206 in previous studies. Accordingly, the analysis of neoplastic and matched normal lung tissues reveals that miR-206 downregulation in lung tumors correlates, in most cases, with higher cyclin D1 levels. Moreover, gain-of-function experiments with cancer-derived cell lines and with in vitro transformed cells indicate that miR-206-mediated cyclin D1 repression is directly coupled to growth inhibition. Altogether, our data highlight a novel activity for miR-206 in skeletal muscle differentiation and identify cyclin D1 as a major target that further strengthens the tumor suppressor function proposed for miR-206

Virulence factors of Salmonella ser. Enteritidis strains isolated in Italy from food-borne outbreaks

Twelve Salmonella ser. Enteritidis strains phage type 4 isolated in Italy from different food-borne outbreaks were characterized for the expression of different virulence traits, for antibiotic resistance, and for plasmid DNA profile. All the twelve S. Enteritidis strains were able to invade and multiply within HeLa cell monolayers, even if at a lower efficiency if compared to an invasive Shigella flexneri strain. The strains were not hemolytic and produced only a moderate-level cytotoxic effect on HeLa cell monolayers. Moreover, all the strains examined produced mannose-sensitive hemagglutination with chicken erythrocytes but were not able to adhere to tissue culture cells. The strains did not produce the hydroxamate-type siderophore aerobactin or the specific ferric-aerobactin receptor. The S. Enteritidis strains were resistant only to spectinomycin, and eleven strains harbored a 38 MDa non-conjugative plasmid, while one strain harbored a 64 MDa conjugative plasmid which carried a colicinogenic activity-encoding locus. The uniformity of antibiotic resistance pattern, of the plasmid DNA content, and of the virulence factors produced indicated that the S. Enteritidis clinical isolates examined are clonally-relate

Renal ultrastructural findings in Anderson-Fabry disease

Anderson-Fabry disease (AFd) is caused by an X-linked inborn error in the glycosphingoLipid metabolic pathway due to an enzymatic defect in a lysosomal hydrolase: alpha-galactosidase A. The defect results in the progressive accumulation of neutral glycosphingolipids in most body fluids and several tissues. The clinical manifestations of AFd are related to organ damage and, obviously, are more severe in hemizygous males than in heterozygous females. In the third decade of life, the course of the disease involves severe deterioration of kidney function progressing to end-stage renal failure. All kind of cells of renal structures are filled with glycosphingolipid deposits. Electron microscopic studies document typical intracytoplasmic osmiophilic bodies with a characteristic "zebra" or "onion-skin" appearance due to concentric lamellation of alternating clear and dark layers. Clinical interest in Fabry patients is related to recent advances in treatment with an intravenous specific enzyme to modify the biochemical error of the glycosphingolipid catabolic pathway

A comparative prospective study of two available solutions for kidney and liver preservation

Abstract: Background. Viaspan (University of Wisconsin [UW]) solution is the gold standard for abdominal organ preservation. Celsior (CEL) is an extracellular-type, low-potassium, low-viscosity solution, initially used for heart and lung preservation. We have performed a prospective multicenter study to compare the role of these cold-storage solutions on kidney and liver recovery after transplantation. Patients and Methods. From March 15, 2000 to December 31, 2001, 441 (172 CEL and 269 UW) renal transplants (RT) and 175 (79 CEL and 96 UW) liver transplants (LT) were included in the study. Results. Perfusate volume used was significantly lower in the UW group, being 4,732+/-796 mL versus 5,826+834 mL in the CEL group (P<0.001). In LT, median total bilirubin serum levels were significantly higher at 5 and 7 posttransplant days in the UW group (90.6 and 92.3 mumol/L, respectively) as compared with CEL (51.3 and 63.4 mumol/L, respectively). After LT, primary nonfunction (PNF) rates in the CEL and UW groups were 3.8% and 4.2% (P=NS) respectively, with 1-year graft and patient survival being 83.3% versus 85.4% (P=NS) and 89.9% versus 90.6% (P=NS). After RT, delayed graft function (DGF) rates were 23.2% and 22.7% (P=NS), respectively; PNF rates were 1.9% and 1.7% (P=NS) respectively, with 1-year graft and patient survival being 92.3% versus 94.2% (P=NS) and 99.4% versus 97.7% (P=NS). Conclusions. CEL solution was shown to be as effective as UW in both liver and kidney preservation. In LT patients, biliary function recovery is significantly better in the CEL group. CEL solution represents an efficacious option in multiorgan harvesting

Outcome of pregnancy after organ transplantation: a retrospective survey in Italy

The number of women who decide to have a child after organ transplantation has increased. We determined the outcomes of 67 pregnancies of women who had undergone kidney, liver or heart transplantation. All recipients had been maintained on immunosuppressive therapy before and during pregnancy. Pregnancy complications at term were observed in 17 out of 67 women (25%), hypertension being the most frequent complication (16.17%). Two transplant rejections were reported. Sixty-eight infants were delivered (including one pair of twins); five women had two pregnancies at term. Twenty-eight miscarriages (29.2%) were recorded. Of these 68 babies (including the pair of twins), 40 (58.8%) were born at term and 28 (41.2%) before term. The babies were followed-up for 2 months to 13 years. According to our previous experience, our study shows that patients who have undergone organ transplantation can give birth to healthy infants as long as they are monitored accurately during pregnancy

A comparative prospective study of two available solutions for kidney and liver preservation

Abstract: Background. Viaspan (University of Wisconsin [UW]) solution is the gold standard for abdominal organ preservation. Celsior (CEL) is an extracellular-type, low-potassium, low-viscosity solution, initially used for heart and lung preservation. We have performed a prospective multicenter study to compare the role of these cold-storage solutions on kidney and liver recovery after transplantation. Patients and Methods. From March 15, 2000 to December 31, 2001, 441 (172 CEL and 269 UW) renal transplants (RT) and 175 (79 CEL and 96 UW) liver transplants (LT) were included in the study. Results. Perfusate volume used was significantly lower in the UW group, being 4,732+/-796 mL versus 5,826+834 mL in the CEL group (P<0.001). In LT, median total bilirubin serum levels were significantly higher at 5 and 7 posttransplant days in the UW group (90.6 and 92.3 mumol/L, respectively) as compared with CEL (51.3 and 63.4 mumol/L, respectively). After LT, primary nonfunction (PNF) rates in the CEL and UW groups were 3.8% and 4.2% (P=NS) respectively, with 1-year graft and patient survival being 83.3% versus 85.4% (P=NS) and 89.9% versus 90.6% (P=NS). After RT, delayed graft function (DGF) rates were 23.2% and 22.7% (P=NS), respectively; PNF rates were 1.9% and 1.7% (P=NS) respectively, with 1-year graft and patient survival being 92.3% versus 94.2% (P=NS) and 99.4% versus 97.7% (P=NS). Conclusions. CEL solution was shown to be as effective as UW in both liver and kidney preservation. In LT patients, biliary function recovery is significantly better in the CEL group. CEL solution represents an efficacious option in multiorgan harvesting

Outcome of pregnancy after organ transplantation: a retrospective survey in Italy.

Pregnancy post transpant is a very importan problem in the life of transplant wome