16 research outputs found
Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds.
The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases
QualitĂ microbiologica delle acque per emodialisi: quali i fattori di rischio? [Microbiological quality of hemodialysis water: what are the risk factors?]
Introduzione Un paziente in dialisi entra in contatto settimanalmente con unâingente quantitĂ dâacqua tramite il bagno
di dialisi, in media 350 litri. Ă pertanto essenziale che questa soluzione abbia unâelevata qualitĂ e purezza. Scopo del
nostro studio Ăš stato monitorare nel tempo la qualitĂ microbiologica delle acque dellâemodialisi, al fine di individuare
eventuali fattori che possano influenzarla.
Metodi Abbiamo effettuato da Gennaio 2015 a Ottobre 2017 uno studio cross-sectional raccogliendo le acque delle
apparecchiature dialitiche presso lâAOU Careggi. I campioni raccolti in maniera asettica e da tecnici specializzati, sono
stati trasportati sotto ghiaccio a 4°C al Laboratorio di Rischio Biologico dellâAzienda USL Toscana Centro per le analisi
di laboratorio.
Risultati Sono stati raccolti 126 campioni di acqua. Coliformi, E. coli, Staphylococcus aureus, enterococchi sono
risultati negativi in tutti i campioni. Pseudomonas aeruginosa Ăš risultata positiva in un solo campione. Sia per le CFU a
37°C che a 22°C la tipologia di macchinario rappresenta lâunico fattore di rischio statisticamente significativo (OR
15.21 e OR 10.25 rispettivamente): i macchinari SDS hanno un rischio decisamente piĂč alto di risultare positivi per le
CFU a 37°C e 22°C.
Conclusioni Ă necessario monitorare costantemente il sistema di trattamento delle acque di dialisi e questo ancor piĂč
nel caso di dispositivi con sistema SDS che, a causa del loro utilizzo discontinuo, possono essere soggetti piĂč
frequentemente, come dimostrato nel nostro studio, a maggiore contaminazione.
PAROLE CHIAVE: sorveglianza, emodialisi, infezioniBACKGROUND:
A dialyzed patient weekly gets in touch with a large amount of water (on average 350 liters) through the dialysis bath. It is therefore essential that this solution would have a high quality and purity. The aim of our study was to monitor the microbiological quality of the hemodialysis water in order to identify possible factors that could affect it.
METHODS:
We conducted a cross-sectional study from January 2015 to October 2017 collecting the dialysis water in AOU Careggi. Samples were aseptically collected by specialized technicians and then transported under ice at 4° C to the Laboratory of Biological Hazards of USL Toscana Centro for laboratory analyses.
RESULTS:
126 water samples were collected. Coliforms, E. coli, Staphylococcus aureus, enterococci were not detected. Pseudomonas aeruginosa was found in only one sample. Both for CFU at 37° C and at 22° C, the type of device represented the only statistically significant risk factor (OR 15.21 and OR 10.25 respectively): SDS devices had a significantly higher risk of being positive for CFU at 37° C and 22° C.
CONCLUSIONS:
As our study demonstrated, the system producing dialysis water must be constantly monitored, especially in cases of SDS devices which may be subjected more frequently to a higher contamination, due to their discontinuous use.
Copyright by SocietĂ Italiana di Nefrologia SIN, Rome, Italy
Liver haploinsufficiency of RuvBL1 causes hepatic insulin resistance and enhances hepatocellular carcinoma progression
RuvBL1 is an AAA+ ATPase whose expression in hepatocellular carcinoma (HCC) correlates with a poor prognosis. In vitro models suggest that targeting RuvBL1 could be an effective strategy against HCC. However, the role of RuvBL1 in the onset and progression of HCC remains unknown. To address this question, we developed a RuvBL1hep+/â mouse model and evaluated the outcome of DENâinduced liver carcinogenesis up to 12âmonths of progression. We found that RuvBL1 haploinsufficiency initially delayed the onset of liver cancer, due to a reduced hepatocyte turnover in RuvBL1hep+/â mice. However, RuvBL1hep+/âmice eventually developed HCC nodules that, with aging, grew larger than in the control mice. Moreover, RuvBL1hep+/â mice developed hepatic insulin resistance and impaired glucose homeostasis. We could determine that RuvBL1 regulates insulin signaling through the Akt/mTOR pathway in liver physiology in vivo as well as in normal hepatocytic and HCC cells in vitro. Whole transcriptome analysis of mice livers confirmed the major role of RuvBL1 in the regulation of hepatic glucose metabolism. Finally, RuvBL1 expression was found significantly correlated to glucose metabolism and mTOR signaling by bioinformatic analysis of human HCC sample from the publicly available TGCA database. These data uncover a role of RuvBL1 at the intersection of liver metabolism, hepatocyte proliferation and HCC development, providing a molecular rationale for its overexpression in liver cancer
Recommended from our members
Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds.
The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases
Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds
The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases
Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds
The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases