RESUMO
Polycomb proteins maintain cell identity by repressing the expression of developmental regulators specific for other cell types. Polycomb repressive complex-2 (PRC2) catalyzes trimethylation of histone H3 lysine-27 (H3K27me3). Although repressed, PRC2 targets are generally associated with the transcriptional initiation marker H3K4me3, but the significance of this remains unclear. Here, we identify a class of short RNAs, approximately 50-200 nucleotides in length, transcribed from the 5' end of polycomb target genes in primary T cells and embryonic stem cells. Short RNA transcription is associated with RNA polymerase II and H3K4me3, occurs in the absence of mRNA transcription, and is independent of polycomb activity. Short RNAs form stem-loop structures resembling PRC2 binding sites in Xist, interact with PRC2 through SUZ12, cause gene repression in cis, and are depleted from polycomb target genes activated during cell differentiation. We propose that short RNAs play a role in the association of PRC2 with its target genes.
Assuntos
RNA/metabolismo , Proteínas Repressoras/metabolismo , Transcrição Gênica , Animais , Sequência de Bases , Células Cultivadas , Cromatina/genética , Cromatina/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Histonas/genética , Histonas/metabolismo , Lisina/metabolismo , Camundongos , Dados de Sequência Molecular , Neurônios/citologia , Neurônios/fisiologia , Conformação de Ácido Nucleico , Proteínas do Grupo Polycomb , Regiões Promotoras Genéticas , RNA/química , RNA/genética , Proteínas Repressoras/genética , Linfócitos T/citologia , Linfócitos T/fisiologiaRESUMO
Very preterm birth is associated with increased cardiovascular diseases and changes in myocardial structure. The current study aimed to investigate the impact of endothelial colony-forming cell (ECFC) treatment on heart morphological changes in the experimental model of neonatal high oxygen (O2 )-induced cardiomyopathy, mimicking prematurity-related conditions. Sprague-Dawley rat pups exposed to 95% O2 or room air (RA) from day 4 (P4) to day 14 (P14) were randomized to receive (jugular vein) exogenous human cord blood ECFC or vehicle at P14 (n = 5 RA-vehicle, n = 8 RA-ECFC, n = 8 O2 -vehicle and n = 7 O2 -ECFC) and the hearts collected at P28. Body and heart weights and heart to body weight ratio did not differ between groups. ECFC treatment prevented the increase in cardiomyocyte surface area in both the left (LV) and right (RV) ventricles of the O2 group (O2 -ECFC vs. O2 -vehicle LV: 121 ± 13 vs. 179 ± 21 µm2 , RV: 118 ± 12 vs. 169 ± 21 µm2 ). In O2 rats, ECFC treatment was also associated with a significant reduction in interstitial fibrosis in both ventricles (O2 -ECFC vs. O2 -vehicle LV: 1.07 ± 0.47 vs. 1.68 ± 0.41% of surface area, RV: 1.01 ± 0.74 vs. 1.77 ± 0.67%) and in perivascular fibrosis in the LV (2.29 ± 0.47 vs. 3.85 ± 1.23%) but in not the RV (1.95 ± 0.95 vs. 2.74 ± 1.14), and with increased expression of angiogenesis marker CD31. ECFC treatment had no effect on cardiomyocyte surface area or on tissue fibrosis of RA rats. Human cord blood ECFC treatment prevented cardiomyocyte hypertrophy and myocardial and perivascular fibrosis observed after neonatal high O2 exposure. ECFC could constitute a new regenerative therapy against cardiac sequelae caused by deleterious conditions of prematurity.
Assuntos
Cardiomiopatias/terapia , Células Endoteliais/transplante , Células Progenitoras Endoteliais/transplante , Oxigênio/toxicidade , Transplante de Células-Tronco/métodos , Animais , Animais Recém-Nascidos , Cardiomiopatias/etiologia , Células Cultivadas , Células Endoteliais/metabolismo , Células Progenitoras Endoteliais/metabolismo , Humanos , Masculino , Miócitos Cardíacos/patologia , Miócitos Cardíacos/fisiologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos , Ratos Sprague-Dawley , RegeneraçãoRESUMO
Chronic nonspecific low back pain is common and one of the most disabling conditions in the world. There is moderate evidence that chronic low back pain patients present altered functional connectivity in areas related to pain processing. Quantitative sensory testing is a way of clinical measure of these alterations. Although there is not enough evidence, there are some reports that electroacupuncture is supposedly more effective in relieving pain than acupuncture because the addition of electric current could optimize the effects of traditional technique. Thus, the objective of this randomized clinical trial was to verify if electroacupuncture treatment reduces pain and changes quantitative sensory testing responses in patients with chronic nonspecific low back pain. Patients were evaluated before and after 10 sessions regarding pain (11-point numerical rating pain scale) and quantitative sensory testing (pressure pain threshold, temporal summation, and conditioned pain modulation). There were 1 treatment group (electroacupuncture (EA)) and three different control groups (CTR 1, CTR 2, and CTR 3). A total of 69 patients participated in the study. No significant differences were found in pain intensity or quantitative sensory testing responses when comparing electroacupuncture group to the three control groups. There was a significant reduction in both resting and movement pain intensity in groups EA, CTR 1, and CTR3. Although ten sessions of electroacupuncture have diminished pain intensity in both resting and movement, it could not change significantly quantitative sensory testing and diminish central sensitization in patients with chronic nonspecific low back pain. The implications of this study involve the fact that, maybe, in chronic nonspecific low back pain, electroacupuncture should be associated with other treatments that target central sensitization.
RESUMO
The local structure of Na-Al-P-O-F glasses, prepared by a novel sol-gel route, was extensively investigated by advanced solid-state NMR techniques. 27Al{19F} rotational echo double resonance (REDOR) results indicate that the F incorporated into aluminophosphate glass is preferentially bonded to octahedral Al units and results in a significant increase in the concentration of six-coordinated aluminum. The extent of Al-F and Al-O-P connectivities are quantified consistently by analyzing 27Al{31P} and 27Al{19F} REDOR NMR data. Two distinct types of fluorine species were identified and characterized by various 19F{27Al}, 19F{23Na}, and 19F{31P} double resonance experiments, which were able to support peak assignments to bridging (Al-F-Al, -140 ppm) and terminal (Al-F, -170 ppm) units. On the basis of the detailed quantitative dipole-dipole coupling information obtained, a comprehensive structural model for these glasses is presented, detailing the structural speciation as a function of composition.
RESUMO
Vitreous samples were prepared in the (100 - x)% NaPO(3)-x% MoO(3) (0
RESUMO
Physical activity modulates inflammation and immune response in both normal and pathologic conditions. We investigated whether regular and moderate exercise before the induction of experimental sepsis reduces the risk of lung and distal organ injury and survival. One hundred twenty-four BALB/c mice were randomly assigned to two groups: sedentary (S) and trained (T). Animals in T group ran on a motorized treadmill, at moderate intensity, 5% grade, 30 min/day, 3 times a week for 8 wk. Cardiac adaptation to exercise was evaluated using echocardiography. Systolic volume and left ventricular mass were increased in T compared with S group. Both T and S groups were further randomized either to sepsis induced by cecal ligation and puncture surgery (CLP) or sham operation (control). After 24 h, lung mechanics and histology, the degree of cell apoptosis in lung, heart, kidney, liver, and small intestine villi, and interleukin (IL)-6, KC (IL-8 murine functional homolog), IL-1ß, IL-10, and number of cells in bronchoalveolar lavage (BALF) and peritoneal lavage (PLF) fluids as well as plasma were measured. In CLP, T compared with S groups showed: 1) improvement in survival; 2) reduced lung static elastance, alveolar collapse, collagen and elastic fiber content, number of neutrophils in BALF, PLF, and plasma, as well as lung and distal organ cell apoptosis; and 3) increased IL-10 in BALF and plasma, with reduced IL-6, KC, and IL-1ß in PLF. In conclusion, regular and moderate exercise before the induction of sepsis reduced the risk of lung and distal organ damage, thus increasing survival.