610 research outputs found
Extracellular vesicles: A therapeutic option for liver fibrosis
Extracellular vesicles (EVs) are a heterogeneous population of small membrane vesicles released by all types of cells in both physiological and pathological conditions. EVs shuttle different types of molecules and are able to modify the behavior of target cells by various mechanisms of action. In this review, we have summarized the papers present in the literature, to our acknowledge, that reported the EV effects on liver diseases. EVs purified from serum, stem cells, and hepatocytes were investigated in different experimental in vivo models of liver injury and in particular of liver fibrosis. Despite the different EV origin and the different types of injury (toxic, ischemic, diet induced, and so on), EVs showed an anti-fibrotic effect. In particular, EVs had the capacities to inhibit activation of hepatic stellate cells, one of the major players of liver fibrosis development; to reduce inflammation and apoptosis; to counteract the oxidative stress; and to increase hepatocyte proliferation, contributing to reducing fibrosis and ameliorating liver function and morphology
Longitudinal Structure Functions in Decaying and Forced Turbulence
In order to reliably compute the longitudinal structure functions in decaying
and forced turbulence, local isotropy is examined with the aid of the isotropic
expression of the incompressible conditions for the second and third order
structure functions. Furthermore, the Karman-Howarth-Kolmogorov relation is
investigated to examine the effects of external forcing and temporally
decreasing of the second order structure function. On the basis of these
investigations, the scaling range and exponents of the longitudinal
structure functions are determined for decaying and forced turbulence with the
aid of the extended-self-similarity (ESS) method. We find that 's are
smaller, for , in decaying turbulence than in forced turbulence. The
reasons for this discrepancy are discussed. Analysis of the local slopes of the
structure functions is used to justify the ESS method.Comment: 15 pages, 16 figure
Molecular Pathways Modulated by Mesenchymal Stromal Cells and Their Extracellular Vesicles in Experimental Models of Liver Fibrosis
Human Liver Stem Cell-Derived Extracellular Vesicles Target Hepatic Stellate Cells and Attenuate Their Pro-fibrotic Phenotype
Liver fibrosis occurs in response to chronic liver injury and is characterized by an excessive deposition of extracellular matrix. Activated hepatic stellate cells are primarily responsible for this process. A possible strategy to counteract the development of hepatic fibrosis could be the reversion of the activated phenotype of hepatic stellate cells. Extracellular vesicles (EVs) are nanosized membrane vesicles involved in intercellular communication. Our previous studies have demonstrated that EVs derived from human liver stem cells (HLSCs), a multipotent population of adult stem cells of the liver with mesenchymal-like phenotype, exert in vivo anti-fibrotic activity in the liver. However, the mechanism of action of these EVs remains to be determined. We set up an in vitro model of hepatic fibrosis using a human hepatic stellate cell line (LX-2) activated by transforming growth factor-beta 1 (TGF-β1). Then, we investigated the effect of EVs obtained from HLSCs and from human bone marrow-derived mesenchymal stromal cells (MSCs) on activated LX-2. The incubation of activated LX-2 with HLSC-EVs reduced the expression level of alpha-smooth muscle actin (α-SMA). Conversely, MSC-derived EVs induced an increase in the expression of pro-fibrotic markers in activated LX-2. The analysis of the RNA cargo of HLSC-EVs revealed the presence of several miRNAs involved in the regulation of fibrosis and inflammation. Predictive target analysis indicated that several microRNAs (miRNAs) contained into HLSC-EVs could possibly target pro-fibrotic transcripts. In particular, we demonstrated that HLSC-EVs shuttled miR-146a-5p and that treatment with HLSC-EVs increased miR-146a-5p expression in LX-2. In conclusion, this study demonstrates that HLSC-EVs can attenuate the activated phenotype of hepatic stellate cells and that their biological effect may be mediated by the delivery of anti-fibrotic miRNAs, such as miR-146a-5p
Nonimmunological alterations of glomerular filtration by s-PAF in the rat kidney
Nonimmunological alterations of glomerular filtration by s-PAF in the rat kidney. Rat kidneys were isolated and perfused with a cell-free perfusion buffer containing 4% albumin. Infusion of platelet activating factor (s-PAF) into the isolated perfused kidney caused a dose-dependent fall in renal vascular resistance (RVR): 12 ± 6% at 10nM s-PAF, 18 ± 3% at 100nM s-PAF and 20 ± 7% at 1 µM. s-PAF. Glomerular filtration rate fell by 32 ± 5% at 10nM, 38 ± 6% at 100nM, and 52 ± 10% at 1 µM. s-PAF (50nM) increased urinary protein excretion after 20 minutes. Because GFR fell to a greater extent than RVR, possible changes in glomerular permeability after s-PAF treatment were assessed morphologically using native ferritin. After s-PAF treatment (100nM), the number of ferritin particles/µm2 increased from 1.2 ± 0.9 (control) to 795 ± 69 in the glomerular basement membrane (GBM) and from 0.2 ± 0.06 (control) to 98 ± 29 in lamina rara externa (LRE). To quantitate changes in fixed anionic charges, polyethylenimine (PEI) was quantitated morphologically in GBM. No significant change between s-PAF treated and untreated kidneys was seen. s-PAF did not alter the sialoglycoprotein pattern in the perfused kidney as assessed by lysozyme staining. These results are in contrast to findings with s-PAF in vivo where in addition to increased glomerular permeability, a reduction of fixed anionic charges is seen. Thus, these results help to differentiate a dual mechanism of s-PAF: 1) a direct action of s-PAF on glomerular epithelial and vascular cells and, 2) an indirect action of s-PAF on glomerular structures via stimulation of release of inflammatory mediators from circulatory cells
Extracellular Vesicles as Biomarkers of Acute Graft-vs.-Host Disease After Haploidentical Stem Cell Transplantation and Post-Transplant Cyclophosphamide
Statistics of Dissipation and Enstrophy Induced by a Set of Burgers Vortices
Dissipation and enstropy statistics are calculated for an ensemble of
modified Burgers vortices in equilibrium under uniform straining. Different
best-fit, finite-range scaling exponents are found for locally-averaged
dissipation and enstrophy, in agreement with existing numerical simulations and
experiments. However, the ratios of dissipation and enstropy moments supported
by axisymmetric vortices of any profile are finite. Therefore the asymptotic
scaling exponents for dissipation and enstrophy induced by such vortices are
equal in the limit of infinite Reynolds number.Comment: Revtex (4 pages) with 4 postscript figures included via psfi
Role of Lefty in the anti tumor activity of human adult liver stem cells
Recent studies demonstrated that factors derived from embryonic stem cells inhibit the tumorigenicity of a variety of cancer cell lines. Embryonic stem cell-secreted Lefty, an inhibitor of Nodal-signalling pathway, was implicated in reprogramming cancer cells. Whether adult stem cells exhibited similar properties has not been explored. The aim of the present study was to investigate whether the conditioned medium (CM) derived from adult stem cells influence in vitro and in vivo tumor growth by a Nodal-dependent pathway. In particular we compared the anti-tumor effect of CM from human liver stem cells (HLSC) with that of bone marrow-derived mesenchymal stem cells (MSC). We found that HLSC-CM inhibited the in vitro growth and promoted apoptosis in HepG2 cells that expressed a deregulated Nodal pathway. The effect of HLSC-CM was related to the presence of Lefty A in the CM of HLSC. Silencing Lefty A in HLSC or Lefty A blockade with a blocking peptide abrogated the anti-proliferative and pro-apoptotic effect of HLSC-CM. Moreover, the administration of human recombinant Lefty A protein mimicked the effect of HLSC-CM indicating that Nodal pathway is critical for the growth of HepG2. At variance of HLSC, bone marrow-derived MSC did not express and release Lefty A and the MSC-CM did not exhibited an anti-tumor activity in vitro, but rather stimulated proliferation of HepG2. In addition, the intra-tumor administration of HLSC-CM was able to inhibit the in vivo growth of HepG2 hepatoma cells implanted subcutaneously in SCID mice. At variance, HLSC-CM derived from Lefty A silenced HLSC was unable to inhibit tumor growth. In conclusion, the results of present study suggest that Lefty A may account for the tumor suppressive activity of HLSC as a result of an inhibition of the Nodal-signalling pathway by a mechanism similar to that described for embryonic stem cells
Extracellular vesicles from human plasma for biomarkers discovery: Impact of anticoagulants and isolation techniques
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