Nanocarriers delivering prodrugs are a way of improving in vivo effectiveness and efficiency. For therapeutic efficacy, the prodrug must hydrolyze to its parent drug after administration. Based on the fact that the hydrolysis is impeded by steric hindrance and improved by sufficient polarity, in this study, we proposed the PTX-S-S-VE, the conjugation of paclitaxel (PTX) to vitamin E (VE) through a disulfide bridge. This conjugate possessed the following advantages: first, it can be encapsulated in the VE/VE2-PEG2000/water nanoemulsions because of favorable hydrophobic interactions; second, the nanoemulsions had a long blood circulation time; finally, the concentrated glutathione in the tumor microenvironment could cleave the disulfide bond to weaken the steric hindrance and increase the polarity, promoting the hydrolysis to PTX and increasing the anticancer activity. It was demonstrated in vitro that the hydrolysis of PTX-S-S-VE was enhanced and the cytotoxicity was increased. In addition, PTX-S-S-VE had greater anticancer activity against the KB-3-1 cell line tumor xenograft and the tumor size was smaller after the 4th injection. The present result suggests a new way, use of reduction, to improve the in vivo anticancer activity of a prodrug for nanocarrier delivery by unshielding the ester bond and taking off the steric block.

Six thiophenes were isolated and purified from ethanol extract of the roots of Echinops latifolius Tausch. Their structures were identified on the basis of spectral data. Among them, 5-(3-hydroxmethyl-3-isovaleroyloxyprop-1-ynyl)-2,2'-bithiophene (6) is a new compound, and 5-(3-hydroxy-4-isovaleroyloxybut-1-ynyl)-2,2'-bithiophene (5) was isolated from this plant for the first time.

The main aim of this systematic review was to analyse and compare the clinical efficacy and safety of metronidazole, vancomycin and fidaxomicin in the therapy of C. difficile infection. Methods: Systematic review and meta-analysis of the literature using Bayesian mixed treatment comparison. Results: Nine studies were included in the mixed-treatment comparison. Our meta-analysis showed that clinical cure was more likely with fidaxomicin compared to vancomycin and metronidazole, however the differences were not significant. (odds ratios [95% CI]: fidaxomicin vs. vancomycin 1.19 [0.82-1.66]; vancomycin vs. metronidazole 1.69 [0.93-2.82] and fidaxomicin vs. metronidazole 2.00 [0.99-3.66]). Fidaxomicin therapy was significantly more efficacious than vancomycin and metronidazole in endpoints of recurrence (odds ratios [95% CI]: fidaxomicin vs. vancomycin 0.47 [0.33-0.65]; vancomycin vs. metronidazole 0.91 [0.44-1.69] and fidaxomicin vs. metronidazole 0.43 [0.19-0.85]) and sustained cure (odds ratios [95% CI]: fidaxomicin vs. vancomycin 1.77 [1.35-2.28]; vancomycin vs. metronidazole 1.49 [0.92-2.30]; and fidaxomicin vs. metronidazole 2.64 [1 .50-4.35]. There was no significant difference between fidaxomicin, vancomycin and metronidazole in safety endpoints. ConClusions: Fidaxomicin was the most efficacious therapeutic alternative in lowering the rate of recurrent C. difficile infections.objeCtives: C. difficile is the leading cause of antibiotic associated infectious nosocomial diarrhoea. A limited number of new pharmaceutical products have been developed and registered in past decades for the treatment of C. difficile infection.

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A new triterpenoid saponin, 3-O-[(3-O-alpha-l-arabinofuranosyl-2-O-beta-d-galactopyranosyl)-beta-d-glucuronopyranosyl]-21,22-di-O-angeloyl-R1-barrigenol (1), together with four known triterpenoids, have been isolated from the husks of Xanthoceras sorbifolia Bunge. Their structures were elucidated based on chemical and spectral analysis. Among them, 1 was found to have activity of inhibiting the proliferation of six human tumour cell lines (IC50 10-40 mug/ml).