Numerical study on the start and unstart phenomena in a scramjet inlet-isolator model.

Inlet unstart and buzz in scramjet engines must be prevented for the stable operation of the engines. In the present study, the characteristics of the inlet start, unstart and buzz phenomena in a scramjet engine inlet model are investigated using numerical analysis with the RANS-based OpenFOAM solver. The results for the inlet start case with a small computational domain that includes only the inlet-isolator part are in good agreement with existing numerical and experimental results. However, for the inlet unstart case, the computational domain must be wide enough to consider the interactions between the upstream of the inlet and the internal flow of the inlet to predict the inlet unstart and buzz phenomena in the inlet test model. The present results show fairly good agreement with existing experimental results with the buzz phenomenon. The effects of boundary layer profiles on the buzz oscillation frequency and amplitude are also addressed.

Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling.

BACKGROUND: The aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937. METHODOLOGY/PRINCIPAL FINDINGS: Icariside II blocked the growth U937 cells in a dose- and time-dependent manner. In this anti-proliferation process, this herb compound rendered the cells susceptible to apoptosis, manifested by enhanced accumulation of sub-G1 cell population and increased the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Icariside II was able to activate caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) in a time-dependent manner. Concurrently, the anti-apoptotic proteins, such as bcl-x(L) and survivin in U937 cells, were downregulated by Icariside II. In addition, Icariside II could inhibit STAT3 phosphorylation and function and subsequently suppress the activation of Janus activated kinase 2 (JAK2), the upstream activators of STAT3, in a dose- and time-dependent manner. Icariside II also enhanced the expression of protein tyrosine phosphatase (PTP) SH2 domain-containing phosphatase (SHP)-1, and the addition of sodium pervanadate (a PTP inhibitor) prevented Icariside II-induced apoptosis as well as STAT3 inactivation in STAT3 positive U937 cells. Furthermore, silencing SHP-1 using its specific siRNA significantly blocked STAT3 inactivation and apoptosis induced by Icariside II in U937 cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that via targeting STAT3-related signaling, Icariside II sensitizes U937 cells to apoptosis and perhaps serves as a potent chemotherapeutic agent for AML.

Inhibition of c-Jun N-terminal kinase and nuclear factor κ B pathways mediates fisetin-exerted anti-inflammatory activity in lipopolysccharide-treated RAW264.7 cells.

Although fisetin, a natural flavonoid, was known to inhibit proliferation, carcinogenesis and inflammation, the underlying anti-inflammatory mechanism of fistein still remains unclear. Thus, in the present study, the anti-inflammatory mechanism of fisetin was investigated in association with mitogen-activated protein kinase (MAPK) and nuclear factor κ B (NF-κB) pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophages. We found that fisetin significantly reduced the nitrate oxide (NO) production and also inhibited the expression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) at protein and mRNA levels in LPS-stimulated cells. Consistently, fisetin significantly reduced the LPS-stimulated secretion of proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor α (TNF-α). Furthermore, fisetin suppressed the activation of nuclear factor κ B (NF-κB) and the phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal regulated kinase (ERK) and p38 MAPK in LPS-treated RAW264.7 cells. Overall, our findings demonstrate that fisetin exerted anti-inflammatory activity via inactivation of JNK and NF-κB in LPS-stimulated macrophage cells.

Protective effect of Bojungbangdocktang on cisplatin-induced cytotoxicity and apoptosis in MCF-10A breast endothelial cells.

Although cisplatin has been extensively used as a cancer chemotherapeutic agent for the treatment of various human cancers, it causes significant side effects such as nephrotoxicity and hepatotoxicity due to lethal bystander damage to normal cells. Thus, in the current study, we investigated the Oriental herbal medicine Bojungbangdocktang (BJBDT), as we reported previously its anti-angiogenic activity at nontoxic concentrations that could prevent cisplatin-induced toxicity and apoptosis in human normal breast epithelial cell MCF-10A, but not in MCF-7 and MDA MB-231 breast cancer cells. BJBDT protected cisplatin-induced cytotoxicity in MCF-10A cells and potentiated cytotoxicity and MMP loss in MCF-7 cells. Also, 4',6-diamidino-2-phenylindole (DAPI) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed that BJBDT reduced cisplatin-induced apoptotic bodies in MCF-10A cells compared with cisplatin-treated control. Consistently, BJBDT attenuated the apoptotic portion sub-G1 DNA contents as well as blocked the activation of caspase-3 and -9 and poly(ADP-ribose)polymerase (PARP) cleavage in cisplatin-treated MCF-10A cells. Taken together, our findings suggest that BJBDT can protect cisplatin-induced cytotoxicity and apoptosis in normal MCF-10A breast cells as a cancer chemopreventive agent.