Omentum acts as a regulatory organ controlling skeletal muscle repair of mdx mice diaphragm.

Duchenne muscular dystrophy is a lethal X-linked muscle wasting disease due to mutations of the dystrophin gene leading to distinct susceptibility to degeneration and fibrosis among skeletal muscles. This study aims at verifying whether intense mdx diaphragm remodeling could be attributed to influences from the omentum, a lymphohematopoietic tissue rich in progenitor cells and trophic factors. Mdx omentum produces growth factors HGF and FGF and increased amounts of VEGF with pleiotropic actions upon muscular progenitors and myoblast differentiation. Histology revealed that the absence of the omentum reduced inflammation and collagen deposition in the diaphragm. The diaphragm from omentectomized mdx mice presents impaired repair with a predominance of collagen type I deposition, decreased muscle regeneration and a reduction in collagen type IV and indication of altered basal lamina integrity in the diaphragm. Omentectomy further reduced inflammatory infiltration and NFκ-B activation but a change in the pattern of muscle inflammation with low numbers of the F4/80+CD206+ M-2 macrophage subset. Although omentectomized mice had high levels of Pax7, myogenin and TNF-α, the percentage of myofibers undergoing regeneration was low thus suggesting that a lack of the omentum halts the muscle differentiation program. Such results support that omentum exerts a regulatory function inducing an inflammatory process that favors regeneration and inhibits fibrosis selectively in the diaphragm muscle thus being a potential site for therapeutic interventions in DMD.

Enlarged colitogenic T cell population paradoxically supports colitis prevention through the B-lymphocyte-dependent peripheral generation of CD4(+)Foxp3(+) Treg cells.

Intestinal inflammation can be induced by the reconstitution of T/B cell-deficient mice with low numbers of CD4(+) T lymphocytes depleted of CD25(+)Foxp3(+) regulatory T cells (Treg). Using RAG-knockout mice as recipients of either splenocytes exclusively depleted of CD25(+) cells or FACS-purified CD4(+)CD25(-)Foxp3(-) T cells, we found that the augmentation of potentially colitogenic naïve T cell numbers in the inoculum was unexpectedly beneficial for the suppression of colon disease and maintenance of immune homeostasis. Protection against T cell-mediated colitis correlated with a significant increment in the frequency of peripherally-induced CD4(+)CD25(+)Foxp3(+) T (pTreg) cells, especially in the mesenteric lymph nodes, an effect that required the presence of B cells and CD4(+)CD25(-)Foxp3(+) cells in physiological proportions. Our findings support a model whereby the interplay between B lymphocytes and a diversified naïve T cell repertoire is critical for the generation of CD4(+)CD25(+)Foxp3(+) pTreg cells and colitis suppression.

Anticonvulsant properties of Euterpe oleracea in mice.

Açai (Euterpe oleracea Mart.), a highly consumed fruit in Amazon, is from a common palm with remarkable antioxidant properties. Because oxidative stress and seizures are intimately linked, this study investigated the potential neuroprotective and anticonvulsant effects of commercial clarified açai juice (EO). EO did not alter spontaneous locomotor activity. Four doses of EO were sufficient to increase latencies to both first myoclonic jerk and first generalized tonic-clonic seizure and significantly decrease the total duration of tonic-clonic seizures caused by pentylenetetrazol administration. Also, electrocortical alterations provoked by pentylenetetrazol were prevented, significantly decreasing amplitude of discharges and frequencies above 50 Hz. EO was also able to completely prevent lipid peroxidation in the cerebral cortex, showing a potent direct scavenging property. These results demonstrate for the first time that E. oleracea significantly protects against seizures and seizure-related oxidative stress, indicating an additional protection for humans who consume this fruit.

Persistent activation of omentum influences the pattern of muscular lesion in the mdx diaphragm.

The mdx (X chromosome-linked muscular dystrophy) mouse develops a multi-staged disorder characterized by muscle degeneration and reactive fibrosis. Skeletal muscles of mdx mice are not equally susceptible to degeneration. The aim of this study was to verify whether the intense remodeling of the mdx diaphragm could be attributed to influences from the peritoneal microenvironment and omentum, a lymphohematopoietic tissue rich in progenitor cells and trophic factors. At ages corresponding to increased muscular regeneration (12 weeks) and activation of fibrosis (24 weeks), the mdx omentum exhibited (1) morphological and functional characteristics of activation with enlarged milk-spots, an accumulation of CD4(+), CD8(+) and CD19(+)B220(+) B lymphocytes; (2) the formation of clusters positive for proliferating cell nuclear antigen, mainly in B220(+)-rich areas organized in a follicular structure with a germinative center without any challenge by external antigen inducers; (3) clusters with cells positive for fibroblast growth factor-2, numerous Sca-1(+)CD3(-)CD19(-)Mac-1(-) progenitor cells and increased CD4(+), CD8(+) and CD3(+)NK1.1(+) cells in the peritoneal cavity. Omentectomy reduced areas with F4/80(+) inflammatory infiltrate the activity of matrix metalloproteases 9 and 2, collagen deposition and areas with regenerating myofibers in the diaphragm. Thus, persistent activation of the omentum influences the pattern of inflammation and regeneration of the mdx diaphragm partly via the activation of progenitor cells and the production of growth factors that influence the physiopathology of the muscular tissue remodeling.