56 research outputs found
Human Mesenchymal Stem Cells Protect Human Islets from Pro-Inflammatory Cytokines
Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. As mesenchymal stem cells (MSCs) possess numerous immunoregulatory properties, we hypothesized that MSCs could protect human islets from pro-inflammatory cytokines. Five hundred human islets were co-cultured with 0.5 or 1.0×106 human MSCs derived from bone marrow or pancreas for 24 hours followed by 48 hour exposure to interferon-γ, tumor necrosis factor-α and interleukin 1β. Controls include islets cultured alone (± cytokines) and with human dermal fibroblasts (± cytokines). For all conditions, glucose stimulated insulin secretion (GSIS), total islet cellular insulin content, islet β cell apoptosis, and potential cytoprotective factors secreted in the culture media were determined. Cytokine exposure disrupted human islet GSIS based on stimulation index and percentage insulin secretion. Conversely, culture with 1.0×106 bMSCs preserved GSIS from cytokine treated islets. Protective effects were not observed with fibroblasts, indicating that preservation of human islet GSIS after exposure to pro-inflammatory cytokines is MSC dependent. Islet β cell apoptosis was observed in the presence of cytokines; however, culture of bMSCs with islets prevented β cell apoptosis after cytokine treatment. Hepatocyte growth factor (HGF) as well as matrix metalloproteinases 2 and 9 were also identified as putative secreted cytoprotective factors; however, other secreted factors likely play a role in protection. This study, therefore, demonstrates that MSCs may be beneficial for islet engraftment by promoting cell survival and reduced inflammation
The Antidiabetic Effect of MSCs Is Not Impaired by Insulin Prophylaxis and Is Not Improved by a Second Dose of Cells
Type 1 diabetes mellitus (T1D) is due to autoimmune destruction of pancreatic beta-cells. Previously, we have shown that intravenously administered bone marrow-derived multipotent mesenchymal stromal cells (MSCs) allows pancreatic islet recovery, improves insulin secretion and reverts hyperglycemia in low doses streptozotocin (STZ)-induced diabetic mice. Here we evaluate whether insulin prophylaxis and the administration of a second dose of cells affect the antidiabetic therapeutic effect of MSC transplantation. Insulitis and subsequent elimination of pancreatic beta-cells was promoted in C57BL/6 mice by the injection of 40 mg/kg/day STZ for five days. Twenty-four days later, diabetic mice were distributed into experimental groups according to if they received or not insulin and/or one or two doses of healthy donor-derived MSCs. Three and half months later: glycemia, pancreatic islets number, insulinemia, glycated hemoglobin level and glucose tolerance were determined in animals that did not received exogenous insulin for the last 1.5 months. Also, we characterized MSCs isolated from mice healthy or diabetic. The therapeutic effect of MSC transplantation was observed in diabetic mice that received or not insulin prophylaxis. Improvements were similar irrespective if they received one or two doses of cells. Compared to MSCs from healthy mice, MSCs from diabetic mice had the same proliferation and adipogenic potentials, but were less abundant, with altered immunophenotype and no osteogenic potential
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Heat Shock Protein 101 Effects in A. Thaliana: Genetic Variation, Fitness and Pleiotropy in Controlled Temperature Conditions.
The Hsp100/ClpB heat shock protein family is ancient and required for high temperature survival, but natural variation in expression and its phenotypic effects is unexplored in plants. In controlled environment experiments, we examined the effects of variation in the Arabidopsis cytosolic AtHsp101 (hereafter Hsp101). Ten wild-collected ecotypes differed in Hsp101 expression responses across a 22 to 40 degrees C gradient. Genotypes from low latitudes expressed the least Hsp101. We tested fitness and pleiotropic consequences of varying Hsp101 expression in \u27control\u27 vs. mild thermal stress treatments (15/25 degrees C D/N vs. 15/25 degrees D/N plus 3 h at 35 degrees C 3 days/week). Comparing wild type and null mutants, wt Columbia (Col) produced approximately 33% more fruits compared to its Hsp101 homozygous null mutant. There was no difference between Landsberg erecta null mutant NIL (Ler) and wt Ler; wt Ler showed very low Hsp101 expression. In an assay of six genotypes, fecundity was a saturating function of Hsp101 content, in both experimental treatments. Thus, in addition to its essential role in acquired thermal tolerance, Hsp101 provides a substantial fitness benefit under normal growth conditions. Knocking out Hsp101 decreased fruit production, days to germination and days to bolting, total dry mass, and number of inflorescences; it increased transpiration rate and allocation to root mass. Root : total mass ratio decayed exponentially with Hsp101 content. This study shows that Hsp101 expression is evolvable in natural populations. Our results further suggest that Hsp101 is primarily an emergency high-temperature tolerance mechanism, since expression levels are lower in low-latitude populations from warmer climates. Hsp101 expression appears to carry an important trade-off in reduced root growth. This trade-off may select for suppressed expression under chronically high temperatures
Acaricidal activity of flavonoids extract of Borago officinalis L. (Boraginaceae) against brown dog tick, Rhipicephalus sanguineus (Latreille, 1806)
International audienceBorago officinalis L. (Boraginaceae) is a plant of the Boraginaceae family, used in Algeria for food and medicinal purposes. This study reports the effect of flavonoids extracted from the aerial part of Borago officinalis L. (Boraginaceae) on the larvae and engorged adult females of the brown dog tick Rhipicephalus sanguineus (Latreille, 1806) using adults immersion test (AIT) and larval immersion test (LIT). For this purpose, the larvae and engorged female of Rhipicephalus sanguineus (Latreille, 1806) were exposed to serial dilutions of flavonoids extract (50 mg/ml, 25 mg/ml, 12.5 mg/ml and 6.25 mg/ml) using ``dipping method'' in vitro. The plant extract was obtained by fractionation using appropriate solvents. The extraction yield is 22% with a flavonoids concentration equal to 129.12 mu g equivalent of quercetin/ml of the extract. The chromatographic analysis by high performance thin layer chromatography (HPTLC) reveals the presence of gallic acid, vanillic acid, kaempferol, dihydroxybenzoic and quercetin. The results obtained show that the flavonoids extract of Borago officunalis L. (Boraginaceae) considerably reduces the oviposition and the hatching rate of the eggs of Rhipicephalus sanguineus (Latreille, 1806) and was shown to be toxic against newly hatched larvae of Rhipicephalus sanguineus (Latreille, 1806) (P < 0.05)
Acaricidal activity of flavonoids extract of Borago officinalis L. (Boraginaceae) against brown dog tick, Rhipicephalus sanguineus (Latreille, 1806)
International audienceBorago officinalis L. (Boraginaceae) is a plant of the Boraginaceae family, used in Algeria for food and medicinal purposes. This study reports the effect of flavonoids extracted from the aerial part of Borago officinalis L. (Boraginaceae) on the larvae and engorged adult females of the brown dog tick Rhipicephalus sanguineus (Latreille, 1806) using adults immersion test (AIT) and larval immersion test (LIT). For this purpose, the larvae and engorged female of Rhipicephalus sanguineus (Latreille, 1806) were exposed to serial dilutions of flavonoids extract (50 mg/ml, 25 mg/ml, 12.5 mg/ml and 6.25 mg/ml) using ``dipping method'' in vitro. The plant extract was obtained by fractionation using appropriate solvents. The extraction yield is 22% with a flavonoids concentration equal to 129.12 mu g equivalent of quercetin/ml of the extract. The chromatographic analysis by high performance thin layer chromatography (HPTLC) reveals the presence of gallic acid, vanillic acid, kaempferol, dihydroxybenzoic and quercetin. The results obtained show that the flavonoids extract of Borago officunalis L. (Boraginaceae) considerably reduces the oviposition and the hatching rate of the eggs of Rhipicephalus sanguineus (Latreille, 1806) and was shown to be toxic against newly hatched larvae of Rhipicephalus sanguineus (Latreille, 1806) (P < 0.05)
Characterization and antibacterial activity of gelatin-based film incorporated with Arbutus unedo L. fruit extract on Sardina pilchardus
Gelatin-based films incorporated with Arbutus unedo fruit extract (AFE) were prepared and characterized. LC-DAD analysis demonstrated that the most abundant phenolic compounds in AFE were procyanidin B2 and gallic acid. The incorporation of AFE in gelatin tested film (TF) caused a remarkable decrease in water vapor permeability (5.01 × 10–9 g.mm/h.cm2.Pa) compared to control films (CF). FTIR analyses presented a broadening of amide A and I bands in the spectrum corresponding to the tested film. Films were used to coat samples on fresh fillets of Sardina pilchardus intentionally inoculated with Staphylococcus aureus, Listeria monocytogenes, and Pseudomonas aeruginosa. Fish samples were stored refrigerated for 12 days; TF exhibited important antimicrobial activity against the tested bacteria, especially against S. aureus. The obtained results will encourage the use of gelatin-based film containing AFE extract in active food packaging systems to control surface contamination by foodborne pathogenic microorganisms. Novelty impact statement: A. unedo extract (AFE) decreased gelatin water vapor permeability and contributed to the formation of hydrogen bonds between the phenolic compounds and the protein matrix. Active gelatin films were able to exert a remarkable antibacterial effect against S. aureus, L. monocytogenes, and P. aeruginosa, intentionally inoculated into sardine fillets. This study demonstrated that the application of gelatin-based film containing AFE on fresh sardine fillets could have the potential in controlling the growth of pathogenic and spoilage bacteria
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