Stem Cell-Derived Exosomes as Nanotherapeutics for Autoimmune and Neurodegenerative Disorders.

To dissect therapeutic mechanisms of transplanted stem cells and develop exosome-based nanotherapeutics in treating autoimmune and neurodegenerative diseases, we assessed the effect of exosomes secreted from human mesenchymal stem cells (MSCs) in treating multiple sclerosis using an experimental autoimmune encephalomyelitis (EAE) mouse model. We found that intravenous administration of exosomes produced by MSCs stimulated by IFNγ (IFNγ-Exo) (i) reduced the mean clinical score of EAE mice compared to PBS control, (ii) reduced demyelination, (iii) decreased neuroinflammation, and (iv) upregulated the number of CD4+CD25+FOXP3+ regulatory T cells (Tregs) within the spinal cords of EAE mice. Co-culture of IFNγ-Exo with activated peripheral blood mononuclear cells (PBMCs) cells in vitro reduced PBMC proliferation and levels of pro-inflammatory Th1 and Th17 cytokines including IL-6, IL-12p70, IL-17AF, and IL-22 yet increased levels of immunosuppressive cytokine indoleamine 2,3-dioxygenase. IFNγ-Exo could also induce Tregs in vitro in a murine splenocyte culture, likely mediated by a third-party accessory cell type. Further, IFNγ-Exo characterization by deep RNA sequencing suggested that IFNγ-Exo contains anti-inflammatory RNAs, where their inactivation partially hindered the exosomes potential to induce Tregs. Furthermore, we found that IFNγ-Exo harbors multiple anti-inflammatory and neuroprotective proteins. These results not only shed light on stem cell therapeutic mechanisms but also provide evidence that MSC-derived exosomes can potentially serve as cell-free therapies in creating a tolerogenic immune response to treat autoimmune and central nervous system disorders.

Distinct palmitoylation events at the amino-terminal conserved cysteines of Env7 direct its stability, localization, and vacuolar fusion regulation in S. cerevisiae.

Palmitoylation at cysteine residues is the only known reversible form of lipidation and has been implicated in protein membrane association as well as function. Many palmitoylated proteins have regulatory roles in dynamic cellular processes, including membrane fusion. Recently, we identified Env7 as a conserved and palmitoylated protein kinase involved in negative regulation of membrane fusion at the lysosomal vacuole. Env7 contains a palmitoylation consensus sequence, and substitution of its three consecutive cysteines (Cys(13)-Cys(15)) results in a non-palmitoylated and cytoplasmic Env7. In this study, we further dissect and define the role(s) of individual cysteines of the consensus sequence in various properties of Env7 in vivo. Our results indicate that more than one of the cysteines serve as palmitoylation substrates, and any pairwise combination is essential and sufficient for near wild type levels of Env7 palmitoylation, membrane localization, and phosphorylation. Furthermore, individually, each cysteine can serve as a minimum requirement for distinct aspects of Env7 behavior and function in cells. Cys(13) is sufficient for membrane association, Cys(15) is essential for the fusion regulatory function of membrane-bound Env7, and Cys(14) and Cys(15) are redundantly essential for protection of membrane-bound Env7 from proteasomal degradation. A role for Cys(14) and Cys(15) in correct sorting at the membrane is also discussed. Thus, palmitoylation at the N-terminal cysteines of Env7 directs not only its membrane association but also its stability, phosphorylation, and cellular function.

Cellulose production by Gluconacetobacter kakiaceti GM5 in two batch process using vinasse as culture media.

The present study was conducted to evaluate the cellulose production by Gluconacetobacter kakiaceti GM5 by means of two aerobic treatments: the static discontinuous fermentation process (treatment 1) and the discontinuous fermentation process in a rotary shaker (treatment 2). All these experiments were carried out using vinasse as experimental culture media (VM) and were compared with standard media containing glucose at 2% (standard medium (SM)). A sample of each treatment was extracted every 24 h over a period of 168 h. The maximum rates of cellulose produced in treatment 1 using SM added up to 3.63 ± 0.18 g l(-1), and to 4.15 ± 0.16 g l(-1) when VM was used. The amount of cellulose produced in treatment 2 using SM was 2.95 ± 0.09 g l(-1) (which suggests an increase of 37%), and added up to 1.84 ± 0.07 g l(-1) when using VM. A better global yield of both treatments in terms of sugar consumption after 168 h was obtained when using VM: 32% in treatment 1, whereas in treatment 2 it was 9%. A 20% decrease on vinasse COD (Chemical Oxygen Demand) values was found to be yet another important advantage of working with this strain.

Calidad de vida y conducta de enfermedad en pacientes con Diabetes Mellitus tipo II / Quality of life and behavior of disease in patients with Diabetes Mellitus type II

El propósito de esta investigación consistió en estudiar la calidad de vida y la conducta de enfermedad en personas con diabetes y observar si existe relación entre ellas. Para ello se aplicó el cuestionario SF-36 y el IBQ a 74 pacientes con edades comprendidas entre los 45 y 65 años diagnosticados con diabetes mellitus tipo II, no insulinodependientes. Se evidenció deterioro importante en la calidad de vida de estos pacientes, principalmente en aquellos componentes relacionados con la salud física. La conducta de enfermedad puntuó en el rango medio en todas sus dimensiones, aproximándose a un nivel alto la hipocondriasis general. Se encontraron correlaciones inversas entre la función física, con percepción psicológica versus somática de la enfermedad. La salud mental correlacionó también de forma negativa con distorsión afectiva, negación de los problemas e irritabilidad. La relación existente entre las dimensiones evaluadas permite una aproximación al planteamiento de patrones de respuesta a la enfermedad, que redundan en la calidad de vida del paciente con diabetes.

The intention of this study was to study the quality of life and the conduct of disease in people with diabetes and to observe if relation among them exists. For it is was applied to questionnaire SF-36 and the IBQ to 74 patients with ages between the 45 and 65 years diagnosed with diabetes mellitus type II. Important deterioration in the quality of life of these patients was demonstrated, mainly in those components related to the physical health. The disease conduct scored in the average rank in all its dimensions, coming near at a high level the general hipocondriasis. Were inverse correlations between the physical function, with psychological perception versus somatic of the disease. The mental health also correlated of negative form with affective distortion, negation of the problems and irritability. The existing relation between the evaluated dimensions allows an approach to the...