36 research outputs found

    Androgen Receptor Drives Cellular Senescence

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    The accepted androgen receptor (AR) role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS) and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor

    Postulated Vasoactive Neuropeptide Autoimmunity in Fatigue-Related Conditions: A Brief Review and Hypothesis

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    Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity

    Recent progress of optical functional nanomaterials based on organoboron complexes with β-diketonate, ketoiminate and diiminate

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    The synthesis and application of organoboron complexes are a highly relevant topic owng to their unique characteristics. Based on their emissive properties, these complexes have been used to make novel optical materials and devices; boron β-diketonate is a simple and robust organoboron complex. From a series of recent studies, unique and versatile optical properties have been reported. In this review, we introduce the results of primarily recent studies on boron diketonate and related compounds containing polymers and particularly explain their optical properties. Initially, the multi-emission of boron diketonate derivatives and its application to biotechnology are explained. Next, the formation of nanostructures and its emission properties are demonstrated. The modulation of optical properties by mechanical stress is also presented. Finally, recent progress in the development of solid-emissive materials are shown with boron diketonates and their derivatives, which have aggregation-induced emission properties. The versatility of boron diketonates as a building block for the preparation of functional optical materials is the focus of this review
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