No abstract

BackgroundVoriconazole has been used in the treatment and prophylaxis of invasive fungal infections (IFIs) while its wide use was limited by some frequent adverse events, especially neurotoxicity, hepatotoxicity and even renal disruption. The aim of this study was to comprehensively compare voriconazole-induced toxicity, including tolerability, neurotoxicity, visual toxicity, hepatotoxicity and nephrotoxicity with the composite of other antifungals commonly used in clinic.MethodsBibliography databases were searched to select randomized controlled trials providing information about the incidence of toxicity referred above. A total of 4122 patients from 16 studies were included in the meta-analysis.ResultsAnalysis of individual types of toxicity showed that there was a significant difference between voriconazole and the composite of other antifungal agents. The primary outcome, the tolerability of voriconazole was slightly inferior (OR = 1.71, 95% CI = 1.21–2.40, P = 0.002) and it is noteworthy that the probabilities of neurotoxicity and visual toxicity were around twice higher and six-fold for voriconazole compared with the counterpart (OR = 1.99, 95% CI = 1.05–3.75, P = 0.03 and OR = 6.50, 95% CI = 2.93–14.41, P < 0.00001, respectively). Hepatotoxicity was more common in voriconazole group (OR = 1.60, 95% CI = 1.17–2.19, P = 0.003) whereas its pooled risk of nephrotoxicity was about half of the composite of other five antifungal agents (OR = 0.46, 95% CI = 0.26–0.84, P = 0.01).ConclusionOur analysis has revealed differences in multiple types of toxicity induced by VRC versus other antifungals and quantified the corresponding pooled risks, which could provide an alternative for patients with a certain antifungal intolerance and help the clinician to select the optimal intervention.Electronic supplementary materialThe online version of this article (10.1186/s12879-017-2913-8) contains supplementary material, which is available to authorized users.

Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in particular drug-resistant cancer, is of great importance. The aim of the present study was to explore the potential of a next-generation taxoid, SB-T-121205, in modulating the proliferation, migration and invasion of paclitaxel-resistant human breast cancer cells (MCF-7/PTX) and further evaluate the underlying molecular mechanisms. The results of MTT assay showed that SB-T-121205 has much higher potency to human breast cancer cells (MCF-7/S, MCF-7/PTX and MDA-MB-453 cells) than paclitaxel, while that the non-tumorigenic human bronchial epithelial cells (BEAS-2B) were slightly less sensitive to SB-T-121205 than paclitaxel. Flow cytometry and western blot methods revealed that SB-T-121205 induced cell cycle arrest at the G2/M phase and apoptosis in MCF-7/PTX cells through accelerating mitochondrial apoptotic pathway, resulting in reduction of Bcl-2/Bax ratio, as well as elevation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) levels. Moreover, SB-T-121205 changed epithelial-mesenchymal transition (EMT) property, and suppressed migration and invasion abilities of MCF-7/PTX cells. Additionally, SB-T-121205 exerted antitumor activity by inhibiting the transgelin 2 and PI3K/Akt pathway. These findings indicate that SB-T-121205 is a potent antitumor agent that promotes apoptosis and also recedes migration/invasion abilities of MCF-7/PTX cells by restraining the activity of transgelin 2 and PI3K/Akt, as well as mitochondrial apoptotic pathway. Such results suggest a potential clinical value of SB-T-121205 in breast cancer treatment.

In this work, effects of direct-current (DC) electric fields on the flame propagation and combustion characteristics of premixed CH 4 /O 2 /N 2 mixtures were experimentally investigated at excess air ratios of 0.8, 1.0, and 1.2, room temperature, and atmospheric pressure. Results show that the existence of the DC electric fields significantly affects the flame propagation and combustion properties. Specifically, the flame shape becomes a prolate spheroid, with the major axis in the electric field direction as a result of the movement of positive ions by the electric body force, and a further increase in the applied voltage distorts the flame front more significantly. Additionally, the flame propagation speed in the electric field direction (S n ) and corresponding unstretched laminar burning velocity (u l ) are increased as the electric field becomes more intense, and this behavior is more pronounced for lean mixtures. Finally, the initial and main combustion durations defined by the pressure evolution profiles are shortened. The peak pressure and peak rate of pressure rise are increased with the increase of the electric field intensity just for lean mixtures. The observation of the laminar burning velocity and pressure evolution behavior substantiates the potential of the electric field in enhancing lean combustion.

No abstract