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Advances in monitoring technology allow blood pressure waveforms to be collected at sampling frequencies of 250–1000 Hz for long time periods. However, much of the raw data are under-analysed. Heart rate variability (HRV) methods, in which beat-to-beat interval lengths are extracted and analysed, have been extensively studied. However, this approach discards the majority of the raw data. Objective: Our aim is to detect changes in the shape of the waveform in long streams of blood pressure data. Approach: Our approach involves extracting key features from large complex data sets by generating a reconstructed attractor in a three-dimensional phase space using delay coordinates from a window of the entire raw waveform data. The naturally occurring baseline variation is removed by projecting the attractor onto a plane from which new quantitative measures are obtained. The time window is moved through the data to give a collection of signals which relate to various aspects of the waveform shape. Main results: This approach enables visualisation and quantification of changes in the waveform shape and has been applied to blood pressure data collected from conscious unrestrained mice and to human blood pressure data. The interpretation of the attractor measures is aided by the analysis of simple artificial waveforms. Significance: We have developed and analysed a new method for analysing blood pressure data that uses all of the waveform data and hence can detect changes in the waveform shape that HRV methods cannot, which is confirmed with an example, and hence our method goes ‘beyond HRV’.

Triptolide is a key anti-inflammatory compound of the Chinese herbal medicine Tripterygium wilfordii Hook. f. (Celastraceae). It also possesses potent antitumor activity. In this study, we show that triptolide is an angiogenesis inhibitor based on various angiogenesis assays. The IC 50 in in vitro assays was 45 nM, which was much lower than the plasma concentrations of triptolide in the rat or human administered with T. wilfordii extracts for treating inflammation. When dosed in vivo, triptolide potently inhibited angiogenesis at 100 nM in Matrigel plug assay. Triptolide at 0.75 mg/kg/day significantly blocked tumor angiogenesis and tumor progression in murine tumorigenesis assay. The underlying mechanism of triptolide correlated with downregulation of proangiogenic Tie2 and VEGFR-2 expression in human umbilical vein endothelial cell by semiquantitative RT-PCR and western blot analysis. Although Tie2 inhibition appeared to be a later event as compared with VEGFR-2, Tie2 overexpression significantly attenuated the inhibitory effect of triptolide on endothelial proliferation and network formation. By contrast, Tie2 knockdown mimicked the inhibitory effect of triptolide on endothelial network formation. Our findings suggest that antitumor action of triptolide is partly via inhibition of tumor angiogenesis by blocking 2 endothelial receptormediated signaling pathways, and triptolide can be a promising antiangiogenic agent.Tripterygium wilfordii Hook. f. (Celastraceae), also known as Thunder God Vine, is a popular herb in China for the treatment of immune-inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, nephritis and asthma. 1 Extracts from T. wilfordii has entered clinical trials for the treatment of rheumatoid arthritis. 2-5 Characterization of the active components present in this plant identified triptolide, a diterpenoid triepoxide, as a key component responsible for most of the immunosuppressive, anti-inflammatory and antiproliferative effects. 6 The content of triptolide was thus used as the quality control marker for most of the extracts and preparations made from T. wilfordii. 7-9 Triptolide itself has also been tested in clinical trials for the treatment of psoriasis vulgaris, 10 diabetic nephropathy 11 and nephritic syndrome 12 in China.Triptolide was first found to have antileukemic activity in 1972. 13 In addition to its potent immunosuppressive and antiinflammatory activities, its antitumor activity has attracted much interest since then. Triptolide exerted antiproliferative and proapoptotic effects on tumor cell lines in vitro, 14-16 restricted tumor growth or shrank tumor in vivo. 17,18 Furthermore, triptolide sensitized tumor cells to other anticancer agents 19 and had synergistic effect with other chemotherapeutic agents in preclinical animal models. 15,18 Although tumor growth and metastasis depend upon angiogenesis, there are only preliminary studies on the effect of triptolide on angiogenesis. 20,21 Antiangiogenic therapy has been increasingly recognized as a pr...

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In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. Silencing USP24 increases the cancer formation by inhibiting cellular apoptosis and increasing cellular proliferation. Epidermal growth factor (EGF) treatment, and the KrasG12D and EGFRL858R mutations decrease USP24 protein stability via EGF- or CDK1-mediated phosphorylation at Ser1616, Ser2047 and Ser2604. Knockdown of USP24 decreases Bax and p300 levels, and reduces Ku70 acetylation, thereby preventing cancer cell apoptosis. In addition, knockdown of USP24 increases cell cycle progression by enhancing the G1–S transition and metaphase–anaphase transition. The molecular mechanism involves a decrease in the USP24 level, which reduces the expression of E2F4 and its partner TFDP1, and thus increases the G1/S transition. In conclusion, the USP24 level was decreased during the early stage of cancer and the mitotic stage of the cell cycle to regulate its substrates p300, Bax, E2F4 and securin, resulting in decreased cell apoptosis and increased cell cycle progression and, thus, cancer formation.