Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6

SummaryQuantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (i.v.) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 × 106 hMSCs were i.v. infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr, but <1000 cells appeared in six other tissues. The hMSCs in lung upregulated expression of multiple genes, with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, i.v. hMSCs, but not hMSCs transduced with TSG-6 siRNA, decreased inflammatory responses, reduced infarct size, and improved cardiac function. I.v. administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest that improvements in animal models and patients after i.v. infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6

Angiotensin II Infusion Induces Marked Diaphragmatic Skeletal Muscle Atrophy

Advanced congestive heart failure (CHF) and chronic kidney disease (CKD) are characterized by increased angiotensin II (Ang II) levels and are often accompanied by significant skeletal muscle wasting that negatively impacts mortality and morbidity. Both CHF and CKD patients have respiratory muscle dysfunction, however the potential effects of Ang II on respiratory muscles are unknown. We investigated the effects of Ang II on diaphragm muscle in FVB mice. Ang II induced significant diaphragm muscle wasting (18.7±1.6% decrease in weight at one week) and reduction in fiber cross-sectional area. Expression of the E3 ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1) and of the pro-apoptotic factor BAX was increased after 24 h of Ang II infusion (4.4±0.3 fold, 3.1±0.5 fold and 1.6±0.2 fold, respectively, compared to sham infused control) suggesting increased muscle protein degradation and apoptosis. In Ang II infused animals, there was significant regeneration of injured diaphragm muscles at 7 days as indicated by an increase in the number of myofibers with centralized nuclei and high expression of embryonic myosin heavy chain (E-MyHC, 11.2±3.3 fold increase) and of the satellite cell marker M-cadherin (59.2±22.2% increase). Furthermore, there was an increase in expression of insulin-like growth factor-1 (IGF-1, 1.8±0.3 fold increase) in Ang II infused diaphragm, suggesting the involvement of IGF-1 in diaphragm muscle regeneration. Bone-marrow transplantation experiments indicated that although there was recruitment of bone-marrow derived cells to the injured diaphragm in Ang II infused mice (267.0±74.6% increase), those cells did not express markers of muscle stem cells or regenerating myofibers. In conclusion, Ang II causes marked diaphragm muscle wasting, which may be important for the pathophysiology of respiratory muscle dysfunction and cachexia in conditions such as CHF and CKD

Substitution levels of fish meal by Arthrospira (=Spirulina) maxima meal in experimental diets for red tilapia fingerlings (Oreochromis sp.)

The high international demand and cost of protein ingredients have led to the increasing need to meet nutritional requirements of animals with national resources. Objective: the objective of th is study was to evaluate three levels of substitution (10, 20, and 30%) of fish meal with Spirulina maxima meal as a protein source in experimental diets for red tilapia fingerlings (Oreochromis sp.). Methods: masculinized fry (average weight: 2.5 ± 0.10 g) were randomly distributed in aerated aquaria with daily water exchange. Four diets were formulated replacing increasing levels of fish meal with Spirulina maxima meal, as follows: 10 (A), 20 (B), 30 (C) and 0% (D, control diet). A commercial diet (E) was also used. All diets were isoproteic (28%) and isocaloric (400 kcal/100 g). Fish were fed two daily rations during 90 days. Weight gain (GP), feed efficiency (EA), protein-efficiency ratio (REP), and feed conversion (FCA) were measured every two weeks. Results were assesses by ANOVA at the end of the test. Results: no significant differences (p>0.05) were observed for GP, EA and REP, indicating a similar efficiency in all diets (A, B, C, D, and E). Treatment C had the best FCA (p0.05) entre a G.P, E.A e R.E.P, indicando uma eficiência similar em todas as dietas (A, B, C, D e E). Para o F.C.A encontraram-se diferencias significativas (p0.05) entre la G.P., E.A. y R.E.P., indicando una eficiencia similar en todas las dietas (A, B, C, D y E). Para el F.C.A., se observaron diferencias significativas (p<0.05), resultando el tratamiento C el de mejor relación alimento consumido – ganancia de peso. Conclusiones: la harina de pescado puede ser substituida por la harina de Spirulina maxima hasta en un 30% en la elaboración de dietas para la alimentación de alevines de tilapia roja

Niveles de sustitución de harina de pescado por harina de Arthrospira (=Spirulina) maxima, en dietas experimentales para alevines de tilapia roja (Oreochromis sp.) Níveis de substituição da farinha de peixe por farinha de Arthrospira (= Spirulina) maxima, em dietas experimentais para alevinos de tilapia vermelha (Oreochromis sp.) Substitution levels of fish meal by Arthrospira (=Spirulina) maxima meal in experimental diets for red tilapia fingerlings (Oreochromis sp.)

Los altos precios de los ingredientes proteicos, así como su demanda, han ocasionado la necesidad cada vez mayor de cubrir los requerimientos nutricionales de los animales con recursos nacionales que proporcionen una fuente de proteína a bajo costo. Objetivo: el objetivo de la presente investigación fue evaluar tres niveles de sustitución (10, 20 y 30%) de harina de pescado por harina de Spirulina maxima como fuente de proteína en dietas experimentales para alevines de tilapia roja (Oreochromis sp.). Métodos: se emplearon alevines masculinizados con peso promedio de 2.5 ± 0.10 g., distribuidos al azar en acuarios con aireación permanente y recambios diarios de agua. Se formularon tres dietas experimentales y una dieta control, con niveles de sustitución de harina de pescado por harina de Spirulina maxima, así: 10 (A), 20 (B), 30 (C) y 0 % (D, dieta control). Todas las dietas fueron isoproteicas (28%) e isocalóricas (400 Kcal/100 g.) y en conjunto con la dieta comercial (E) fueron suministradas a los peces en dos raciones diarias durante 90 días. Se realizaron muestreos quincenales donde se determinaron: ganancia de peso (G.P.), eficiencia alimenticia (E.A.), relación eficiencia-proteína (R.E.P.) y el factor de conversión alimenticia (F.C.A). Al final del ensayo, se compararon entre sí los resultados de cada parámetro mediante un ANOVA a un nivel de significancia del 5 %. Resultados: el análisis no reveló diferencias significativas (p>0.05) entre la G.P., E.A. y R.E.P., indicando una eficiencia similar en todas las dietas (A, B, C, D y E). Para el F.C.A., se observaron diferencias significativas (p<0.05), resultando el tratamiento C el de mejor relación alimento consumido &ndash; ganancia de peso. Conclusiones: la harina de pescado puede ser substituida por la harina de Spirulina maxima hasta en un 30% en la elaboración de dietas para la alimentación de alevines de tilapia roja.<br>Os altos preços dos ingredientes proteicos, assim como sua demanda, tem ocasionado uma necessidade cada vez maior de cobrir os requerimentos nutricionais dos animais com recursos nacionais que proporcionem uma fonte de proteína de baixo custo. Objetivo: o objetivo da presente pesquisa foi avaliar três níveis de substituição (10, 20 e 30%) de farinha de peixe por farinha de Spirulina maxima como fonte de proteína em dietas experimentais para alevinos de tilápia vermelha (Oreochromis sp.). Métodos: Utilizaram-se alevinos masculinizados com peso médio de 2.5 ± 0.10 g, distribuídos ao acaso num aquário com aeração permanente e mudanças diárias de água. Formularam-se três dietas experimentais e a dieta controle, com níveis de substituição de farinha de peixe por farinha de Spirulina maxima de 10 (A), 20(B), 30 (C) e 0 % (D, dieta controle), todas isoproteicas (28%) e isocalóricas (400 Kcal/100 g.) que em conjunto com a dieta comercial (E), foram subministradas aos peixes em dois rações diárias, durante 90 dias. Realizaram-se amostragens a cada 15 dias onde se determinaram: ganho de peso (G.P), eficiência alimentícia (E.A), relação eficiência proteína (R.E.P) e o fator de conversão alimentícia (F.C.A). Ao final do ensaio compararam-se entre sim os resultados de cada parâmetro mediante um ANOVA com um nível de significância de 5%. Resultados: Este analise não revelou diferenças significativas (p>0.05) entre a G.P, E.A e R.E.P, indicando uma eficiência similar em todas as dietas (A, B, C, D e E). Para o F.C.A encontraram-se diferencias significativas (p<0.05), resultando o tratamento C o de melhor relação entre alimento consumido e o ganho de peso. Conclusões: a farinha de peixe pode ser substituída por farinha de Spirulina máxima até um 30% na elaboração de dietas para a alimentação de alevinos de tilápia vermelha.<br>The high international demand and cost of protein ingredients have led to the increasing need to meet nutritional requirements of animals with national resources. Objective: the objective of th is study was to evaluate three levels of substitution (10, 20, and 30%) of fish meal with Spirulina maxima meal as a protein source in experimental diets for red tilapia fingerlings (Oreochromis sp.). Methods: masculinized fry (average weight: 2.5 ± 0.10 g) were randomly distributed in aerated aquaria with daily water exchange. Four diets were formulated replacing increasing levels of fish meal with Spirulina maxima meal, as follows: 10 (A), 20 (B), 30 (C) and 0% (D, control diet). A commercial diet (E) was also used. All diets were isoproteic (28%) and isocaloric (400 kcal/100 g). Fish were fed two daily rations during 90 days. Weight gain (GP), feed efficiency (EA), protein-efficiency ratio (REP), and feed conversion (FCA) were measured every two weeks. Results were assesses by ANOVA at the end of the test. Results: no significant differences (p>0.05) were observed for GP, EA and REP, indicating a similar efficiency in all diets (A, B, C, D, and E). Treatment C had the best FCA (p<0.05). Conclusions: fish meal can be substituted with up to 30% Spirulina maxima meal in the preparation of diets for red tilapia fry