Traumatic brain injury (TBI) is a common cause for cognitive and communication problems, but the molecular and cellular mechanisms are not well understood. Epigenetic modifications, such as microRNA (miRNA) dysregulation, may underlie altered gene expression in the brain, especially hippocampus that plays a major role in spatial learning and memory and is vulnerable to TBI. To advance our understanding of miRNA in pathophysiological processes of TBI, we carried out a time-course microarray analysis of microRNA expression profile in rat ipsilateral hippocampus and examined histological changes, apoptosis and synapse ultrastructure of hippocampus post moderate TBI. We found that 10 out of 156 reliably detected miRNAs were significantly and consistently altered from one hour to seven days after injury. Bioinformatic and gene ontology analyses revealed 107 putative target genes, as well as several biological processes that might be initiated by those dysregulated miRNAs. Among those differentially expressed microRNAs, miR-144, miR-153 and miR-340-5p were confirmed to be elevated at all five time points after TBI by quantitative RT-PCR. Western blots showed three of the predicated target proteins, calcium/calmodulin-dependent serine protein kinase (CASK), nuclear factor erythroid 2-related factor 2 (NRF2) and alpha-synuclein (SNCA), were concurrently down- regulated, suggesting that miR-144, miR-153 and miR-340-5p may play important roles collaboratively in the pathogenesis of TBI-induced cognitive and memory impairments. These microRNAs might serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain.
Epidemiological and animal studies suggest that tea may be protective towards cancers of the GI tract. White tea, the least processed form of tea, contains high levels of polyphenols and, like green tea, is chemopreventive towards heterocyclic amine-initiated colonic aberrant crypt formation in male F344 rats. We examined for the first time the relative effectiveness of white and green tea in suppressing intestinal tumorigenesis in C57BL/6J-Apc(Min/+) (Apc(min)) mice. Each tea was also compared with sulindac, a non-steroidal anti-inflammatory drug known to be highly effective in Apc(min) mice. Male C57BL/6J (+/+) (wild-type) and Apc(min) mice were treated in the drinking water with white tea or green tea (1.5% w/v, 2 min brew-time), 80 p.p.m. sulindac, a combination of 80 p.p.m. sulindac in 1.5% white tea, or pH buffered water. After 12 weeks of treatment, Apc(min) mice given white tea, green tea, or sulindac had significantly fewer tumors than controls (P < 0.05). The protection provided by 1.5% green or white tea was comparable to that provided by 80 p.p.m. sulindac. Mice treated with a combination of white tea plus sulindac had significantly fewer tumors than either treatment alone (P < 0.05). beta-catenin and beta-catenin/Tcf-4 regulated proteins Cyclin D(1) and c-Jun were readily detected in polyps, but markedly reduced in normal-looking intestines of mice treated with both tea and sulindac. This research provides evidence that teas, particularly when administered in combination with sulindac, are highly effective at inhibiting intestinal neoplasia in male Apc(min) mice via direct or indirect effects on the beta-catenin/APC pathway.
Background and Aims-Actin-myosin II motor converts chemical energy into force/motion in muscle and non-muscle cells. The phosphorylation of regulatory light chain (MLC 20 ) is critical to the cytoplasmic functions of these motors. We do not know whether myosin II and actins in the nucleus function as motors to generate relative motion, such as that between RNA polymerase II holoenzyme and DNA, for assembly of the preinitiation complex.
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