Mitochondria-mediated apoptosis was induced by oleuropein in H1299 cells involving activation of p38 MAP kinase.

Lung cancer is the main health threat in the world. Recently, oleuropein has been reported to have potent antioxidant and anticancer activities. However, the antitumor effects of oleuropein on H1299 cells are not well understood. Therefore, the purpose of this paper is tantamount to explore the effects of oleuropein on H1299 cells and its underlying mechanism that may be involved. Oleuropein treatment in H1299 cells resulted in cell cycle distribution at G2 /M arrest and apoptosis in a dose-dependent manner. Mitochondria-mediated apoptosis was verified by the increase in Bax/Bcl-2 ratio, release of cytochrome c, and activation of caspase-3 on oleuropein-induced H1299 cells. In addition, our data also demonstrated that the p38 mitogen-activated protein kinase (MAPK) signaling pathway has a critical role in oleuropein-induced apoptosis. Moreover, we used transcriptome analysis to identify differentially expressed genes (DEGs) in H1299 cells by oleuropein and SB203580 treatment. Many DEGs were annotated to metabolic pathways, cell cycle, pathways in cancer, MAPK signaling pathway by Kyoto Encyclopedia of Genes and Genomes and Gene ontology enrichment methods. Network and expression analysis found that DEGs, including RPS6A5, GADD45A, and MKP, play a key role in the p38 MAPK signaling pathway. In H1299 cells, oleuropein resulted in the expression of numerous genes related to cell signaling, metabolism pathway and directly associated with apoptosis. These results illustrated that oleuropein-induced apoptosis via mitochondrial apoptotic cascade was activated by the p38 MAPK signaling pathway in H1299 cells. Thus, oleuropein as a natural compound and therapeutic drug has potential application value in the treatment of lung cancer.

[Multi-angle Plane-wave Beamforming Algorithm Based on CUDA].

Multi-angle plane-wave beamforming algorithm is the basis of ultra-fast ultrasonic imaging. It can be used to improve the imaging frame rate and resolution of traditional focused ultrasound. However, the existing multi-angle plane-wave technology can not satisfy the real-time imaging requirements due to the huge amount of computation required by CPU. In this paper, We proposed a parallel processing method to reduce the computation time based on compute unified device architecture(CUDA). Simulation analysis and contrast experiment were conducted to verify its performance. Experimental results show that the execution time based on GPU is much less than that based on CPU, thus the computational speed is accelerated significantly to satisfy the demand of ultrafast imaging.

Generic, network schema agnostic sparse tensor factorization for single-pass clustering of heterogeneous information networks.

Heterogeneous information networks (e.g. bibliographic networks and social media networks) that consist of multiple interconnected objects are ubiquitous. Clustering analysis is an effective method to understand the semantic information and interpretable structure of the heterogeneous information networks, and it has attracted the attention of many researchers in recent years. However, most studies assume that heterogeneous information networks usually follow some simple schemas, such as bi-typed networks or star network schema, and they can only cluster one type of object in the network each time. In this paper, a novel clustering framework is proposed based on sparse tensor factorization for heterogeneous information networks, which can cluster multiple types of objects simultaneously in a single pass without any network schema information. The types of objects and the relations between them in the heterogeneous information networks are modeled as a sparse tensor. The clustering issue is modeled as an optimization problem, which is similar to the well-known Tucker decomposition. Then, an Alternating Least Squares (ALS) algorithm and a feasible initialization method are proposed to solve the optimization problem. Based on the tensor factorization, we simultaneously partition different types of objects into different clusters. The experimental results on both synthetic and real-world datasets have demonstrated that our proposed clustering framework, STFClus, can model heterogeneous information networks efficiently and can outperform state-of-the-art clustering algorithms as a generally applicable single-pass clustering method for heterogeneous network which is network schema agnostic.

A Modified 2D Multiresolution Hybrid Algorithm for Ultrasound Strain Imaging.

Ultrasound elastography is an imaging modality to evaluate elastic properties of soft tissue. Recently, 1D quasi-static elastography method has been commercialized by some companies. However, its performance is still limited on high strain level. In order to improve the precision of estimation during high compression, some algorithms have been proposed to expand the 1D window to a 2D window for avoiding the side-slipping. But they are usually more computationally expensive. In this paper, we proposed a modified 2D multiresolution hybrid method for displacement estimation, which can offer an efficient strain imaging with stable and accurate results. A FEM phantom with a stiffer circular inclusion is simulated for testing the algorithm. The elastographic contrast-to-noise rate (CNRe) is calculated for quantitatively comparing the performance of the proposed algorithm with conventional 1D elastography using phase zero estimation and the 1D elastography using downsampled (d-s) baseband signals. Results show that the proposed method is robust and performs similarly as other algorithms in low strain but is superior when high level strain is applied. Particularly, the CNRe of our algorithm is 15 times higher than original method under 4% strain level. Furthermore, the execution time of our algorithm is five times faster than other algorithms.

Oleuropein induced apoptosis in HeLa cells via a mitochondrial apoptotic cascade associated with activation of the c-Jun NH2-terminal kinase.

Oleuropein could inhibit growth and/or induce apoptosis in several cancer cell lines. In this study, we investigate how oleuropein strongly induces apoptotic cell death in HeLa human cervical carcinoma cells. Oleuropein induced HeLa cells apoptosis as demonstrated by induction of a sub-G(1) peak in flow cytometry and apoptosis-related morphological changes observed by fluorescence microscopy after being stained by Hoechst 33324. The results also showed that 150 - 200 µM oleuropein–treated HeLa cells were arrested at the G(2)/M phase. Western blot analysis revealed that the phosphorylated ATF-2, c-Jun NH(2)-terminal kinase (JNK) protein, p53, p21, Bax, and cytochrome c protein in the cytoplasm significantly increased in a dose-dependent manner after treatment of oleuropein for 24 h. Additionally, increasing levels of Bax in response to JNK/SPAK signaling, which formed mitochondrial membrane channels, accounted for releasing of cytochrome c and activation of caspase-9 and -3. SP600125 (20 µM), a JNK(1/2) inhibitor, markedly suppressed the formation of apoptotic bodies and JNK activation induced by oleuropein at 200 µM. Thus, oleuropein-induced apoptosis was activated by the JNK/SPAK signal pathway. The result shows that oleuropein holds promise as a potential chemotherapeutic agent for the treatment of HeLa cells.

Self-assembled, fluorescent polymeric micelles of a graft copolymer containing carbazole for thermo-controlled drug delivery in vitro.

A novel thermosensitive amphiphilic graft copolymer PNIPAAm-g-PCbzEA appending carbazole group was successfully designed and synthesized by the free radical copolymerization of N-isopropylacrylamide with hydrophobic precursor polymers of vinyl-functionalized poly(2-(N-carbazolyl)ethyl acrylate) (PCbzEA) in DMF. The PNIPAAm-g-PCbzEA copolymer was characterized by FTIR, (1)H NMR, GPC analysis, UV-vis spectroscopy and fluorescence spectroscopy. The TEM observation shows that the graft copolymer may self-assemble into polymeric micelles exhibiting a nanospheric morphology within a narrow size range of 30-60 nm in aqueous solution. From the (1)H NMR and FTIR analysis, the polymer micelles are composed of hydrophobic PCbzEA segments as the cores and the hydrophilic PNIPAAm segements as outer shells. The resulting micelles exhibited the temperature sensitivity with a lower critical solution temperature (LCST) of 31.5 degrees C and a critical micelle concentration (CMC) of 12.9 mg/L in water. In the study of drug release, an "on-off" drug release profile was found in response to stepwise temperature changes between 20 and 40 degrees C. The cytotoxicity assays for vero cells shows good biocompatibility of the graft copolymer in vitro.