Conditional double knockout of presenilin-1 and presenilin-2 (cDKO) in forebrain of mice led to brain atrophy, tau hyperphosphorylation, synaptic dysfunction and cognitive deficit. These brain changes recapitulated most of the neurodegenerative phenotypes of Alzheimer's disease (AD). In this report, we have investigated the effects of 4-month calorie restriction (CR) regimen on different phenotypes in cDKO mice. We found that CR improved novel object recognition and contextual fear conditioning memory in the cDKO mice. Histological and biochemical analysis showed that CR attenuated ventricle enlargement, caspase-3 activation and astrogliosis. In addition, the induction of tau hyperphosphorylation in the cDKO mice was reduced by CR, possibly through reduction of p25 accumulation and aberrant CDK5 activation. Finally, DNA microarray analysis demonstrated that CR could increase the expression of neurogenesis related genes and decrease the expression of inflammation related genes in the hippocampus of cDKO mice. The possible molecular mechanisms of the CR effects on alleviating AD pathogenesis have been discussed. 相似文献
Micronuclei tests (MNT) using the Chinese Hamster Ovary (CHO) cells and Chinese Hamster Ovary Mutant cells (XRS5) have been conducted to evaluate the biocompatibility of silicon and titanium plasma-implanted silicon. Pure Si induces high MN ratios of the two cell lines and thus has poor biocompatibility. The MN ratio of CHO cells is higher than background by about 44% and the MN ratio of XRS5 cells is even higher by about 180%, suggesting that most of the cellular DNA damages on the Si wafer are DNA double-strand breaks (DSB) and are efficiently repaired by the nonhomologous end-joining (NHEJ) pathway. The surface biocompatibility of Si can be enhanced by Ti plasma immersion ion implantation (PIII). The altered oxidized species on the Ti plasma-implanted surface block cellular DSB repaired by the NHEJ pathway and decrease the MN ratio of XRS5 cells. By increasing the Ti implantation time and consequently the Ti implant fluence, the oxygen binding energy shifts toward a lower energy and the intensity of the Si peaks corresponding to SiO(2) continually diminishes and even disappear. At the same time, the MN ratios of the two cell lines decrease. Our results suggest that the rest of the DNA damages which cannot be repaired by the NHEJ pathway may be blocked because the surface bonding changes from predominantly Si-O on the 10 min Ti-implanted Si to Ti-O on the 120 min Ti-implanted Si. Our results also suggest that the genotoxicity of cell assay such as MNT and DSB is a valid method to investigate biocompatibility. 相似文献
Radiotherapy is one of the principal modalities of rectal cancer treatment, and the ability to predict radio resistance could
potentially improve survival through a targeted treatment approach. Cyclooxygenase-2 (COX-2) may protect against damage by
irradiation that would justify the use of COX-2 inhibitors. The purpose of this study was to investigate the potential role
of COX-2 in tumor response and outcome of patients with rectal cancer treated preoperatively with radiotherapy. Using immunohistochemistry,
we examined COX-2 expression in 88 surgical specimens of rectal cancer treated preoperatively and in 26 pretherapeutic biopsies.
We tested whether COX-2 expression was correlated with clinico-pathologic parameters and with survival and local recurrence.
COX-2 was expressed in 50% of the pretherapeutic tumor biopsies and in 88.6% of post-irradiated surgical samples. COX-2 expression
was correlated only with enhanced tumor inflammation (p = 0.03) and with tumor volume exceeding 30 cc (p = 0.05). COX-2 was not significantly correlated with patient survival, but none of the patients with COX-2 negative tumors
did recur locally, whereas 80% of patients with local recurrences have COX-2 positive tumors. We conclude that COX-2 expression
is overexpressed in the majority of rectal cancers treated with radiotherapy and likely plays a role in local relapse. 相似文献
The proton conductivities of poly(vinylbenzyl phosphonic acid) (PVBPA) homopolymer and its statistical copolymers with 4‐vinyl pyridine [poly(VBPA‐stat‐4VP)s] are comprehensively studied in this work. Temperature and composition‐dependent “dry” proton conductivities of the copolymers have been determined and the self‐condensation of phosphonic acid groups has been quantified. The results show that the intrinsic proton conductivities of poly(VBPA‐stat‐4VP)s and PVBPA are quite low at 150 °C and exhibit time‐dependent changes due to anhydride formation at elevated temperatures. The effect of polymer composition on proton conduction shows a minimum at a 1:1 molar ratio of proton donor and acceptor groups and is discussed on the basis of the pKa values of the electrolyte species. A trace amount of water significantly increases conductivity probably due to additional hydronium ion diffusion and water bridging effects. Water content and proton conductivities of poly(VBPA‐stat‐4VP)s are determined at different relative humidities. High amounts of water are absorbed at high humidities leading to high proton conductivities.
