Highlights d Arc GAG domain is phosphorylated by CaMKII, which prevents Arc oligomerization d Arc phosphorylation controls the magnitude of mGluRdependent LTD d Arc regulation by CaMKII phosphorylation is required for adaptive learning

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The ovarian system comprises vital organs in females and is of great significance for the maintenance of reproductive potential and endocrine stability. Although complex pathogenesis undoubtedly contributes to ovarian aging, increasing attention is being paid to the extensive influence of oxidative stress. However, the role of oxidative stress in ovarian aging is yet to be fully elucidated. Exploring oxidative stress-related processes might be a promising strategy against ovarian aging. In this review, compelling evidence is shown that oxidative stress plays a role in the etiology of ovarian aging and promotes the development of other ovarian aging-related etiologies, including telomere shortening, mitochondrial dysfunction, apoptosis, and inflammation. In addition, some natural antioxidants such as quercetin, resveratrol, and curcumin have a protective role in the ovaries through multiple mechanisms. These findings raise the prospect of oxidative stress modulator-natural antioxidants as therapeutic interventions for delaying ovarian aging.

Abstract:Wheat is one of the most important crops in the world. Its yield is greatly influenced by global climate change and scarcity of water in the arid and semi-arid areas of the world. So, exploration of gene resources is of importance to wheat breeding in order to improve the crop ability of coping with abiotic stress environment. Wild relatives of wheat are rich repositories of beneficial genes that confer tolerance or resistance not only to drought but also to other environmental stresses. In the present study, the changes in leaf relative water content (RWC), free proline content, and malondialdehyde (MDA) accumulation of five wild wheat species including T. boeticum (YS-1L), T. dicoccum var. dicoccoides (YS-2L), T. araraticum (ALLT), and two cultivated varieties of T. turgidum ssp. durum (MXLK and 87341), with two well-known common wheat cultivars (SH6 and ZY1) possessing strong drought resistance and sensitiveness, respectively, as references were investigated during 3-day water stress and 2-day recovery, in order to assess the drought tolerance of these wild wheat species. The laboratory experiment was conducted under two water regimes (stress and non-stress treatments). Stress was induced to hydroponically grown two weeks old wheat seedlings with 20% PEG 6000. Stress treatment caused a much smaller decrease in the leaf RWC and rise in MDA content in YS-1L compared to the other wheat species. From the data it was obvious that YS-1L was the most drought tolerant among studied species having significantly higher proline and RWC while lower MDA content under water stress conditions. The order of water stress tolerance of these species according to the three parameters is: YS-1L > YS-2L > SH6 > 87341 > ZY1 > MXLK > ALLT. We speculate that the observed drought stress tolerance at a cellular level was associated with the ability to accumulate proline and high water level conservation.

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Silica nanorattles (SNs) have proven to be promising vehicles for drug delivery. In order to further enhance efficacy and minimize adverse effects, active targeted delivery to tumors is necessary. In this work, SNs modified with a tumor specific targeting ligand, folic acid (FA), was used as carrier of doxorubicin (DOX) (DOX-FA-SNs). Drug loading, cytotoxicity and cellular uptake of DOX-FA-SNs in vitro in human cervical carcinoma cells (HeLa cells) were evaluated. DOX-FA-SNs showed a higher cytotoxicity in human cervical carcinoma cells (HeLa cells) than DOX loaded carboxyl (-COOH) and poly(ethylene glycol) (PEG) modified SNs (DOX-COOH-SNs and DOX-PEG-SNs, respectively). However, DOX-FA-SNs showed lower cytotoxicity in folate receptor negative normal mouse fibroblast cells (L929 cells) compared with free DOX. In vivo tumor-targeted fluorescence imaging indicated specific tumor targeting and uptake of FA-SNs in nude mice bearing subcutaneous HeLa cell-derived xenograft tumors. In vivo anti-tumor experiments demonstrated that DOX-FA-SNs (10 mg kg(-1) of DOX) significantly regressed the tumor growth and reduced toxicity compared with free DOX. These results have great significance in developing and optimizing SNs as effective intracellular delivery and specific tumor targeting vehicles.

The Bcl-2 antagonist ABT-737 targets Bcl-2/Bcl-xL, but not Mcl-1, which may confer resistance to this agent in various cancers with high levels of Mcl-1. Here, we showed that the combination of gemcitabine and ABT-737 exhibited synergistic cytotoxicity and induced significant apoptosis in multiple cancer types, including lung, renal, bladder, and prostate cancers. The enhanced apoptosis induced by gemcitabine plus ABT-737 was accompanied by the greater extent of mitochondrial depolarization, caspases-3 activation, and PARP cleavage in 95-D and 5637 cell lines. Importantly, in ABT-737-resistant cancer cells, the interaction between USP9X and Mcl-1, which was increased by ABT-737 treatment, could be disrupted by gemcitabine, thus resulting in enhanced ubiquitination and the subsequent degradation of Mcl-1 and ultimately in the synergism of these two drugs. Moreover, the increased anticancer efficacy of gemcitabine combined with ABT-737 was further validated in a human lung cancer 95-D xenograft model in nude mice. Taken together, our data first showed the synergistic anticancer capabilities achieved by combining gemcitabine and ABT-737 and, second, opened new opportunities to use antiapoptotic Bcl-2 family members, which drive tumor cell resistance in current anticancer therapies, therapeutically. Mol Cancer Ther; 10(7); 1264-75. Ó2011 AACR.