Effect of indomethacin-loaded nanocapsules incorporation in a dentin adhesive resin

Clinical Oral Investigations - The aim of this study was to produce indomethacin-loaded nanocapsules (IndOH-NCs) and evaluate the influence of their incorporation into an adhesive resin....     

Molecular mapping of the regenerative niche in a murine model of myocardial infarction

Adult stem cells are distributed through the whole organism, and present a great potential for the therapy of different types of disease. For the design of efficient therapeutic strategies, it is important to have a more detailed understanding of their basic biological characteristics, as well as of the signals produced by damaged tissues and to which they respond. Myocardial infarction (MI), a disease caused by a lack of blood flow supply in the heart, represents the most common cause of morbidity and mortality in the Western world. Stem cell therapy arises as a promising alternative to conventional treatments, which are often ineffective in preventing loss of cardiomyocytes and fibrosis. Cell therapy protocols must take into account the molecular events that occur in the regenerative niche of MI. In the present study, we investigated the expression profile of ten genes coding for chemokines or cytokines in a murine model of MI, aiming at the characterization of the regenerative niche. MI was induced in adult C57BL/6 mice and heart samples were collected after 24 h and 30 days, as well as from control animals, for quantitative RT-PCR. Expression of the chemokine genes CCL2, CCL3, CCL4, CCL7, CXCL2 and CXCL10 was significantly increased 24 h after infarction, returning to baseline levels on day 30. Expression of the CCL8 gene significantly increased only on day 30, whereas gene expression of CXCL12 and CX3CL1 were not significantly increased in either ischemic period. Finally, expression of the IL-6 gene increased 24 h after infarction and was maintained at a significantly higher level than control samples 30 days later. These results contribute to the better knowledge of the regenerative niche in MI, allowing a more efficient selection or genetic manipulation of cells in therapeutic protocols.     

Long-term memory for aversive training is impaired in Idua(-/-) mice, a genetic model of mucopolysaccharidosis type I

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease that leads to neurodegeneration and neurological deficits, among other pathological and clinical consequences. The aim of the present study was to evaluate neurobehavioral parameters in a genetic mouse model of mucopolysaccharidosis type I (MPS I). During exploration of an open field, adult MPS I (Idua(-/-)) mice showed normal locomotion and anxiety but reduced number of rearings. Idua(-/-) mice performed normally in a novel object recognition memory task and showed normal short-term retention of inhibitory avoidance training. By contrast, long-term retention of inhibitory avoidance was impaired in Idua(-/-) mice. The deficit in inhibitory avoidance memory could not be attributed to reduced footshock reactivity. The results indicate that Idua(-/-) mice present deficits in long-term memory for aversive training and reduced exploratory behavior.     

Aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exhibit high antioxidant capability and promising in vitro antitumor activity

Mushroom extracts are increasingly sold as dietary supplements because of several of their properties, including the enhancement of immune function and antitumor activity. We hypothesized that soluble polar substances present in mushroom extracts may show antioxidant and anticancer properties. This report shows that Brazilian aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exert inhibitory activity against the proliferation of the human tumor cell lines laryngeal carcinoma (Hep-2) and cervical adenocarcinoma (HeLa). Cell viability was determined after using 3 different temperatures (4°C, 22°C, and 50°C) for mushroom extraction. Biochemical assays carried out in parallel indicated higher amounts of polyphenols in the L edodes extracts at all extraction temperatures investigated. The scavenging ability of the 2,2-diphenyl-1-picrylhydrazyl radical showed higher activity for L edodes extracts. Superoxide dismutase–like activity showed no statistically significant difference among the groups for the 2 tested extracts, and catalase-like activity was increased with the L edodes extracts at 4°C. The results for the cytotoxic activity from P sajor-caju extracts at 22°C revealed the half maximal inhibitory concentration values of 0.64% ± 0.02% for Hep-2 and 0.25% ± 0.02% for HeLa. A higher cytotoxic activity was found for the L edodes extract at 22°C, with half maximal inhibitory concentration values of 0.78% ± 0.02% for Hep-2 and 0.57% ± 0.01% for HeLa. Substantial morphological modifications in cells were confirmed by Giemsa staining after treatment with either extract, suggesting inhibition of proliferation and induction of apoptosis with increasing extract concentrations. These results indicate that the aqueous extracts of Brazilian L edodes and P sajor-caju mushrooms are potential sources of antioxidant and anticancer compounds. However, further investigations are needed to exploit their valuable therapeutic uses and to elucidate their modes of action.     

Mesenchymal stem cells combined with an artificial dermal substitute improve repair in full-thickness skin wounds

Autografts represent the gold standard for the treatment of full thickness burns. Factors such as lack of suitable donor sites and poor skin quality, however, have led to the development of artificial dermal substitutes. The investigation of mechanisms leading to enhanced functionality of these skin substitutes has been attracting great attention. This study aimed to investigate the effect of autologous stem cells on the integration and vascularization of a dermal substitute in full-thickness skin wounds, in a murine model. Two cell populations were compared, whole bone marrow cells and cultivated mesenchymal stem cells, isolated from mice transgenic for the enhanced green fluorescent protein, which allowed tracking of the transplanted cells. The number of cells colonizing the dermal substitute, as well as vascular density, were higher in mice receiving total bone marrow and particularly mesenchymal stem cells, than in control animals. The effect was more pronounced in animals treated with mesenchymal stem cells, which located primarily in the wound bed, suggesting a paracrine therapeutic mechanism. These results indicate that combining mesenchymal stem cells with artificial dermal substitutes may represent an important potential modality for treating full thickness burns, even in allogeneic combinations due to the immunoregulatory property of these cells.     

Systemic delivery of adult stem cells improves cardiac function in spontaneously hypertensive rats

1. Heart regeneration after myocardial infarction (MI) can occur after cell therapy, but the mechanisms, cell types and delivery methods responsible for this improvement are still under investigation. In the present study, we evaluated the impact of systemic delivery of bone marrow cells (BMC) and cultivated mesenchymal stem cells (MSC) on cardiac morphology, function and mortality in spontaneously hypertensive rats (SHR) submitted to coronary occlusion. 2. Female syngeneic adult SHR, submitted or not (control group; C) to MI, were treated with intravenous injection of MSC (MI + MSC) or BMC (MI + BM) from male rats and evaluated after 1, 15 and 30 days by echocardiography. Systolic blood pressure (SBP), functional capacity, histology, mortality rate and polymerase chain reaction for the Y chromosome were also analysed. 3. Myocardial infarction induced a decrease in SBP and BMC, but not MSC, prevented this decrease. An improvement in functional capacity and ejection fraction (38 +/- 4, 39 +/- 3 and 58 +/- 2% for MI, MI + MSC and MI + BM, respectively; P < 0.05), as well as a reduction of the left ventricle infarcted area, were observed in rats from the MI + BM group compared with the other three groups. Treated animals had a significantly reduced lesion tissue score. The mortality rate in the C, MI + BM, MI + MSC and MI groups was 0, 0, 16.7 and 44.4%, respectively (P < 0.05 for the MI + MSC and MI groups compared with the C and MI + BM groups). 4. The results of the present study suggest that systemic administration of BMC can improve left ventricular function, functional capacity and, consequently, reduce mortality in an animal model of MI associated with hypertension. We speculate that the cells transiently home to the myocardium, releasing paracrine factors that recruit host cells to repair the lesion.