Flavonoids from Gynostemma pentaphyllum exhibit differential induction of cell cycle arrest in H460 and A549 cancer cells.

Flavonoids, containing mainly kaempferol rhamnohexoside derivatives, were extracted from Gynostemma pentaphyllum (G. pentaphyllum) and their potential growth inhibition effects against H460 non-small cell lung cancer cells was explored and compared to that on A549 cells. The extracted flavonoids were found to exhibit antiproliferation effects against H460 cells (IC50 = 50.2 µg/mL), although the IC50 of H460 is 2.5-fold that of A549 cells (IC50 = 19.8 µg/mL). Further investigation revealed that H460 cells are more susceptible to kaempferol than A549, whereas A549 cell growth is better inhibited by kaempferol rhamnohexoside derivatives as compared with H460. In addition, flavonoids from G. pentaphyllum induced cell cycle arrest at both S and G2/M phases with concurrent modulated expression of the cellular proteins cyclin A, B, p53 and p21 in A549 cells, but not H460. On the contrary, apoptosis and concomitant alteration in balance of BCL-2 and BAX expression as well as activation of caspase-3 were equally affected between both cells by flavonoid treatment. These observations strongly suggest the growth inhibition discrepancy between H460 and A549 following flavonoid treatment can be attributed to the lack of cell cycle arrest in H460 cells and the differences between H460 and A549 cells may serve as contrasting models for further mechanistic investigations.

Bactericidal activity of soymilk fermentation broth by in vitro and animal models.

Soybean fermentation broth (SFB) exhibits potent antibacterial activity against different species of bacteria in in vitro assays and animal models. Four isoflavone compounds-daidzin, genistin, genistein, and daidzein-of SFB were analyzed and quantified by high-performance liquid chromatography. In the in vitro test, daidzin and daidzein had more potent antibacterial activity than genistin. The minimum inhibition concentration values for these bacteria of SFB ranged from 1.25% to 5%, and the minimum bactericidal concentration values of strains ranged from 2.5% to 10%, depending on the species or strain. Vancomycin-resistant Entercoccus faecalis (VRE) strains were also tested for susceptibility to SFB in two species of animal model: the Sprague-Dawley rat and the BALB/c mouse. SFB-fed Sprague-Dawley rats showed excellent elimination efficiency against VRE, close to 99% compared with the phosphate-buffered saline-fed control group. In the BALB/c mouse model, SFB antibacterial activity was 65-80% against VRE compared with the control. In conclusion, SFB contains natural antibacterial substances such as daidzin, genistin, and daidzein that inhibit bacterial growth.

Carbapenem therapy for bacteremia due to extended-spectrum-ß-lactamase-producing Escherichia coli or Klebsiella pneumoniae: implications of ertapenem susceptibility.

A retrospective study was conducted at two medical centers in Taiwan to evaluate the clinical characteristics, outcomes, and risk factors for mortality among patients treated with a carbapenem for bacteremia caused by extended-spectrum-beta-lactamase (ESBL)-producing organisms. A total of 251 patients with bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates treated by a carbapenem were identified. Among these ESBL-producing isolates, rates of susceptibility to ertapenem (MICs ≤ 0.25 µg/ml) were 83.8% and 76.4%, respectively; those to meropenem were 100% and 99.3%, respectively; and those to imipenem were 100% and 97.9%, respectively. There were no significant differences in the critical illness rate (P = 0.1) or sepsis-related mortality rate (P = 0.2) for patients with bacteremia caused by ESBL-producing K. pneumoniae (140 isolates, 55.8%) and E. coli (111 isolates, 44.2%). Multivariate analysis of variables related to sepsis-related mortality revealed that the presence of severe sepsis (odds ratio [OR], 15.9; 95% confidence interval [CI], 5.84 to 43.34; P < 0.001), hospital-onset bacteremia (OR, 4.65; 95% CI, 1.42 to 15.24; P = 0.01), and ertapenem-nonsusceptible isolates (OR, 5.12; 95% CI, 2.04 to 12.88; P = 0.001) were independent risk factors. The patients receiving inappropriate therapy had a higher sepsis-related mortality than those with appropriate therapy (P = 0.002), irrespective of ertapenem, imipenem, or meropenem therapy. Infections due to the ertapenem-susceptible isolates (MICs ≤ 0.25 µg/ml) were associated with a more favorable outcome than those due to ertapenem-nonsusceptible isolates (MICs > 0.25 µg/ml), if treated by a carbapenem. However, the mortality for patients with bacteremic episodes due to isolates with MICs of ≤ 0.5 µg/ml was similar to the mortality for those whose isolates had MICs of >0.5 µg/ml (P = 0.8). Such a finding supports the rationale of the current CLSI 2011 criteria for carbapenems for Enterobacteriaceae.