It has been reported that antimicrobial peptides (AMPs), also known as host-defense peptides, can selectively bind to negatively charged prokaryotic and cancer cell membranes and exert cytotoxicity, without harming normal cells or causing severe drug resistance. We have designed a series of novel cationic AMPs with potent antimicrobial activity against a broad spectrum of bacterial pathogens. In the current study, we evaluated their anticancer potency toward gastric cancer AGS cell line. Cell viability assay

revealed that GW-H1 exhibited the lowest IC50 value (less than 20 mu M). Flow cytometry showed that upon GW-H1 treatment for 0-24 h, apoptotic cell populations of AGS increased in a dose- and time-dependent manner. Western BEZ235 VX 809 blot analysis further revealed that upon treatment for 2-6 h, apoptosis-related caspases-3, 7, 8, 9, and PARP were cleaved and activated, while autophagy-related LC3-II and beclin-1 were concomitantly increased. These results indicated that both apoptosis and autophagy were involved in the early stage of GW-H1-induced AGS cell death. However, upon treatment for 12-24 h, LC3-II began to decrease and cleaved beclin-1 increased in a time-dependent manner,

suggesting that consecutive activation of caspases cleaved beclin-1 to inhibit autophagy, thus enhancing apoptosis at the final stage. These findings provided support for future application of GW-H1 as a potential anticancer agent for gastric cancer treatment.”
“BACKGROUND: Patients with cystic fibrosis (CF) are at increased risk of inspiratory muscle fatigue and respiratory failure. The time constant (tau) of the inspiratory muscle relaxation is a simple bedside test of muscle fatigue. We have compared patients with CF and healthy Ro-3306 nmr controls regarding tau and hypothesized that it is negatively associated with severity of lower airway obstruction. METHODS: For this cross-sectional study, tau after maximal inspiration and spirometric indices (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)) were measured. RESULTS: Fifty-three CF patients (median age 14 y (interquartile range:

11-19.5)) and 53 age- and sex-matched healthy control subjects (14 y (11-19.5)) were recruited. Application of a general linear model revealed that health status (CF vs. non-CF) had a significant effect on tau (P smaller than 0.001), but age group and the interaction of age group with health status did not have significant effects on tau (P = 0.10 and P = 0.71, respectively). Participants with CF had significantly higher tau (253 (188-406)) than control subjects (117 (81-185)) (P smaller than 0.001) and tau was negatively related to FEV1 (r = -0.205; P= 0.031) and FVC (r = -0.294; P = 0.002). CONCLUSION: Patients with CF have higher tau than healthy controls but the correlation of tau with expiratory flow function is modest.