Design, synthesis and biological evaluation of novel diosgenin-benzoic acid mustard hybrids with potential anti-proliferative activities in human hepatoma HepG2 cells.

To discover new lead compounds with anti-tumour activities, in the present study, natural diosgenin was hybridised with the reported benzoic acid mustard pharmacophore. The in vitro cytotoxicity of the resulting newly synthesised hybrids (8-10, 14a-14f, and 15a-15f) was then evaluated in three tumour cells (HepG2, MCF-7, and HeLa) as well as normal GES-1 cells. Among them, 14f possessed the most potential anti-proliferative activity against HepG2 cells, with an IC50 value of 2.26 µM, which was 14.4-fold higher than that of diosgenin (IC50 = 32.63 µM). Furthermore, it showed weak cytotoxicity against GES-1 cells (IC50 > 100 µM), thus exhibiting good antiproliferative selectivity between normal and tumour cells. Moreover, 14f could induce G0/G1 arrest and apoptosis of HepG2 cells. From a mechanistic perspective, 14f regulated cell cycle-related proteins (CDK2, CDK4, CDK6, cyclin D1 and cyclin E1) as well mitochondrial apoptosis pathway-related proteins (Bax, Bcl-2, caspase 9, and caspase 3). These findings suggested that hybrid 14f serves as a promising anti-hepatoma lead compound that deserves further research.

Rotor UAV's Micro-Doppler Signal Detection and Parameter Estimation Based on FRFT-FSST.

The micro-Doppler signal generated by the rotors of an Unmanned Aerial Vehicle (UAV) contains the structural features and motion information of the target, which can be used for detection and classification of the target, however, the standard STFT has the problems such as the lower time-frequency resolution and larger error in rotor parameter estimation, an FRFT (Fractional Fourier Transform)-FSST (STFT based synchrosqueezing)-based method for micro-Doppler signal detection and parameter estimation is proposed in this paper. Firstly, the FRFT is used in the proposed method to eliminate the influence of the velocity and acceleration of the target on the time-frequency features of the echo signal from the rotors. Secondly, the higher time-frequency resolution of FSST is used to extract the time-frequency features of micro-Doppler signals. Moreover, the specific solution methodologies for the selection of window length in STFT and the estimation of rotor parameters are given in the proposed method. Finally, the effectiveness and accuracy of the proposed method for target detection and rotor parameter estimation are verified through simulation and measured data.

(-)-Epicatechin Suppresses Angiotensin II-induced Cardiac Hypertrophy via the Activation of the SP1/SIRT1 Signaling Pathway.

BACKGROUND/AIMS: Flavonol (-)-epicatechin (EPI) is present in high amounts in cocoa and tea products, and has been shown to exert beneficial effects on the cardiovascular system. However, the precise mechanism of EPI on cardiomyocyte hypertrophy has not yet been determined. In this study, we examined whether EPI could inhibit cardiac hypertrophy. METHODS: We utilised cultured neonatal mouse cardiomyocytes and mice for immunofluorescence, immunochemistry, qRT-PCR, and western blot analyses. RESULTS: 1µM EPI significantly inhibited 1µM angiotensin II (Ang II)-induced increase of cardiomyocyte size, as well as the mRNA and protein levels of ANP, BNP and ß-MHC in vitro. The effects of EPI were accompanied with an up-regulation of SP1 and SIRT1, and were abolished by SP1 inhibition. Up-regulation of SP1 could block Ang II-induced increase in cardiomyocyte size, as well as the mRNA and protein levels of ANP, BNP and ß-MHC, and increase the protein levels of SIRT1 in vitro. Moreover, 1 mg/kg body weight/day EPI significantly inhibited mouse cardiac hypertrophy induced by Ang II, which could be eliminated by SP1 inhibition in vivo. CONCLUSION: Our data indicated that EPI inhibited AngII-induced cardiac hypertrophy by activating the SP1/SIRT1 signaling pathway.

Micro-Doppler Signal Time-Frequency Algorithm Based on STFRFT.

This paper proposes a time-frequency algorithm based on short-time fractional order Fourier transformation (STFRFT) for identification of a complicated movement targets. This algorithm, consisting of a STFRFT order-changing and quick selection method, is effective in reducing the computation load. A multi-order STFRFT time-frequency algorithm is also developed that makes use of the time-frequency feature of each micro-Doppler component signal. This algorithm improves the estimation accuracy of time-frequency curve fitting through multi-order matching. Finally, experiment data were used to demonstrate STFRFT's performance in micro-Doppler time-frequency analysis. The results validated the higher estimate accuracy of the proposed algorithm. It may be applied to an LFM (Linear frequency modulated) pulse radar, SAR (Synthetic aperture radar), or ISAR (Inverse synthetic aperture radar), for improving the probability of target recognition.

Dual Response Site Fluorescent Probe for Highly Sensitive Detection of Cys/Hcy and GSH In Vivo through Two Different Emission Channels.

Much research has demonstrated that metabolic imbalances of biothiols are closely associated with the emergence of different types of disease. In view of the significant effect of biothiols, quantitative evaluation and discrimination of intracellular Cys/Hcy and GSH in complex biological environments is very important. In this study, probe CDS-NBD, synthesized by attaching 2,4-dinitrobenzenesulfonate (DNBS, site 1) and nitrobenzoxadiazole (NBD, site 2) as the highly sensitive and selective dual response site for thiols onto the coumarin derivative 7-hydroxycoumarin-4-acetic acid, exhibited large separation of the emission wavelengths, fast response, notable fluorescence enhancement, excellent sensitivity and selectivity to Cys/Hcy and GSH over other biological species. Additionally, CDS-NBD could make a distinction between two different fluorescent signals, GSH (an obvious blue fluorescence) and Cys/Hcy (a mixed blue-green fluorescence). Further study on imaging of Cys/Hcy and GSH in vivo by employing probe CDS-NBD could also be successfully achieved.

Pro-apoptotic and anti-proliferative effects of corn silk extract on human colon cancer cell lines.

Corn silk is an economically and nutritionally significant natural product as it represents a staple food for a large proportion of the world population. This study investigated the anticancer activity of corn silk extract in human colon cancer cells and human gastric cancer cells. Following treatment with corn silk extract, certain apoptosis-related events were observed, including inhibition of cell proliferation, loss of mitochondrial membrane potential (ΔΨm), release of Ca2+ and release of cytochrome c from the mitochondria into the cytosol. Our results revealed that corn silk extract inhibited the proliferation of cancer cells and increased the level of apoptosis in a concentration-dependent manner. Western blot analysis revealed that corn silk extract upregulated the levels of Bax, cytochrome c, caspase-3 and caspase-9, but downregulated the levels of B-cell lymphoma 2. These results suggest that corn silk extract may induce apoptosis through the mitochondria-mediated pathway.