Antioxidant defense system is altered by dietary oxidized lipid in first-feeding rainbow trout (Oncorhynchus mykiss)

International audienceHigh concentrations of n − 3 polyunsaturated fatty acids (PUFA) that are readily susceptible to lipid peroxidative damage are found in fish feeds and in the tissues of fish, especially in early developmental stages. A dietary phospholipid (PL) supply has been shown to be beneficial during these critical stages. The objective of the study was to characterize the response of the antioxidant defense system under dietary prooxidant conditions in presence or absence of dietary PL during early development of rainbow trout. Rainbow trout (Oncorhynchus mykiss) at the first-feeding fry stage (mean weight: 66 ± 2 mg) or at the fingerling stage (mean weight: 1.5 ± 0.4 g) were fed 4 semi-purified diets supplemented with 12% fresh fish oil or 12% oxidized fish oil and 6% soybean lecithin or 6% soybean oil for 4 weeks at 17 °C. At fry stages, rainbow trout fry fed the PL-supplemented diets had a significantly higher final body weight than fry fed the PL-free diets (0.37 ± 0.07 vs. 0.27 ± 0.03 g, respectively). Dietary inclusion of oxidized lipid reduced growth (0.19 ± 0.02 vs. 0.45 ± 0.07 and 2.5 ± 0.6 vs. 4.8 ± 0.6 g, respectively) and increased the mRNA expression of antioxidant enzymes such as glutathione reductase and glutathione S-transferase at both developmental stages. However, dietary control of antioxidant enzyme activities and vitamins was low in rainbow trout fry whereas increased activities of antioxidant enzymes and decreased tocopherol contents were noticed in rainbow trout fingerlings fed oxidized lipid compared to rainbow trout fry fed fresh oil. This resulted in higher content of lipid peroxidation products in rainbow trout fry fed oxidized lipid compared to fish fed fresh lipid whereas this difference was reduced at the fingerling stage. The present study demonstrates that rainbow trout fry are more susceptible to oxidative stress induced by dietary oxidized lipid than rainbow trout fingerlings, possibly due to delayed response or lack of complete development of endogenous antioxidant defense syste

Tau accumulates in Crohn’s disease gut

International audienc

Circulating Klotho associates with cardiovascular morbidity and mortality during hemodialysis

Epub ahead of printBackground: Klotho gene was identified as an aging suppressor. In animals klotho over-expression extends lifespan and defective klotho results in rapid aging and early death. The kidney is the main contributor to circulating klotho levels and during chronic kidney disease, renal klotho gene expression is drastically reduced in animals and humans as well.Objective: We aimed to determine the consequences of a serum klotho defect on cardiovascular morbidity and mortality during chronic dialysis.Design: The ARNOGENE study was designed to prospectively follow a cohort of hemodialysis patients for 2 years without specific intervention. 769 patients were recruited and followed from the end of 2008 until January 2011. 238 patients were analysed due to a technical sample conservation issue with other samples.Results: The median serum klotho was markedly reduced, 360.4 ng/L [IQR176.5] as compared with non-dialysis chronic kidney disease patients or healthy volunteers. Patients with a serum klotho above the first quartile (≥280 ng/L) had a significantly reduced occurrence of outcome combining cardiovascular events and cardiovascular death (OR=0.39; 0.19-0.78, p=0.008) compared to patient with klotho <280 ng/L. This effect persisted (OR=0.86; 0.76-0.99, p=0.03) after adjustment on age, gender, diabetes, cardiac insufficiency, dialysis vintage, and serum hemoglobin, albumin, FGF-23, phosphate and calcium.Conclusions: These results suggest that during chronic hemodialysis, conservation of serum klotho above 280 ng/L is associated with a better 2-yr cardiovascular protection. Thus, a preserved klotho function supports cardiovascular protection and may represent a prognostic tool and therapeutic target for cardiovascular disease

Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis.

International audiencePrimary myelofibrosis is a myeloproliferative neoplasm that is a precursor to myeloid leukemia. Dysmegakaryopoiesis and extramedullary hematopoiesis characterize primary myelofibrosis, which is also associated with bone marrow stromal alterations marked by fibrosis, neoangiogenesis, and osteomyelosclerosis. In particular, contributions to primary myelofibrosis from mesenchymal stromal cells (MSC) have been suggested by mouse studies, but evidence in humans remains lacking. In this study, we show that bone marrow MSCs from primary myelofibrosis patients exhibit unique molecular and functional abnormalities distinct from other myeloproliferative neoplasms and these abnormalities are maintained stably ex vivo in the absence of leukemic cells. Primary myelofibrosis-MSC overexpressed heparin-binding cytokines, including proinflammatory TGFβ1 and osteogenic BMP-2, as well as glycosaminoglycans such as heparan sulfate and chondroitin sulfate. Transcriptome and functional analyses revealed alterations in MSC differentiation characterized by an increased osteogenic potential and a TGFβ1 signaling signature. Accordingly, phospho-Smad2 levels were intrinsically increased in primary myelofibrosis-MSC along with enhanced expression of the master bone regulator RUNX2, while inhibition of the endogenous TGFβ1 receptor TGFβR1 impaired osteogenic differentiation in these MSCs. Taken together, our results define the source of a critical osteogenic function in primary myelofibrosis that supports its pathophysiology, suggesting that combined targeting of both the hematopoietic and stromal cell compartments in primary myelofibrosis patients may heighten therapeutic efficacy. Cancer Res; 75(22); 4753-65. ©2015 AACR

Interleukin-10 modulates the sensitivity of peritoneal B lymphocytes to chemokines with opposite effects on stromal cell-derived factor-1 and B-lymphocyte chemoattractant.

International audienceInterleukin-10 (IL-10) is constitutively produced by peritoneal B1a lymphocytes, and stromal cell-derived factor-1 (SDF-1) by mesothelial cells. Independent studies have shown that both IL-10 and SDF-1 are involved in the persistence of the peritoneal B-lymphocyte compartment. This study shows that IL-10 and SDF-1 act in synergy on peritoneal B lymphocytes. Indeed, autocrine production of IL-10 was absolutely required for all effects of SDF-1 on these cells, including increased proliferation, survival, and chemotaxis. Moreover, adding IL-10 to peritoneal B lymphocytes increased the effects of SDF-1. Neither IL-5, IL-6, nor IL-9 affected the response of peritoneal B lymphocytes to SDF-1. IL-10 was chemokinetic for peritoneal B lymphocytes, increasing their random mobility. It also potentiated the SDF-1-induced reorganization of the cytoskeleton without affecting CXCR4 gene expression by peritoneal B lymphocytes. Despite its chemokinetic properties, IL-10 abolished the migration of peritoneal B lymphocytes in response to B-lymphocyte chemoattractant (BLC), a chemokine targeting B lymphocytes to lymphoid organ follicles. The ability of B1a lymphocytes to produce IL-10 constitutively, combined with the opposite effects of this cytokine on the responses to SDF-1 and BLC, may account for the selective accumulation of B1 lymphocytes in body cavities