The genome sequences of 175 Ebola virus from five districts in Sierra Leone, collected during September–November 2014, show that the rate of virus evolution seems to be similar to that observed during previous outbreaks and that the genetic diversity of the virus has increased substantially, with the emergence of several novel lineages.
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Treatment of EVD with T-705 was associated with prolonged survival and markedly reduced viral load, which makes a compelling case for further randomized controlled trials of T-705 for treating EVD.
The cytolytic peptide melittin (MLT) is an important candidate of anticancer drug owing to its hemolytic properties. Nevertheless, its clinical applications are severely restricted as a result of its nonspecific toxicities like hemolysis. In this work, we reported MLT-loaded zeolitic imidazolate framework-8 (MLT@ZIF-8) nanoparticles (NPs). The formed MLT@ZIF-8 NPs not only possess excellent stability but also efficiently inhibit the hemolysis bioactivity of MLT. Confocal scanning imaging and cytotoxicity experiments revealed that as-synthesized MLT@ZIF-8 NPs exhibit enhanced cellular uptake and cytotoxicity toward cancer cells compared to MLT. The mechanism is well investigated by a series of transcriptome analysis, which indicates that MLT@ZIF-8 NPs can regulate the expression of 3383 genes, and the PI3K/Akt-regulated p53 pathway is involved in MLT@ZIF-8 NPs induced A549 cells apoptosis. Finally, MLT@ZIF-8 NPs exhibit enhanced antitumor activity than free MLT in vivo, while no obvious systemic toxicity has been found. This work emphasizes the great potential of utilizing MOF as a simple and efficient nanoplatform for deliverying cytolytic peptides in cancer treatment, and also the investigation on the antitumor mechanism could provide theoretical support for clinical usage of MLT.
Background: Adipose-derived mesenchymal stem cells (ADMSCs) have attracted widespread interest as cell-based tissue repair systems. To obtain adequate quantities of ADMSCs for therapeutic applications, extensive in vitro expansion is required. However, under current two-dimensional (2D) approaches, ADMSCs rapidly undergo replicative senescence, and cell growth is impeded and stem cell properties are eliminated by mechanisms that are poorly understood. These issues limit the extensive applications of ADMSCs. In this study, we investigated senescence-related changes in mesenchymal stem cells (MSCs) isolated from human adipose tissue in 2D and three-dimensional (3D) cultures. Methods: We studied cell growth over a given period (21 days) to determine if modes of culture were associated with ADMSC senescence. ADMSCs were isolated from healthy females by liposuction surgery and then were grown in 2D and 3D cultures. The cell morphology was observed during cell culture. Every other time of culture, senescence-associated β-galactosidase (SA-β-gal) expression, cell viability, proliferation, and differentiation potential of ADMSCs from 2D and 3D cultures were detected. Also, senescence-and stemness-related gene expression, telomere length, telomerase activity, and energy metabolism of ADMSCs for different culture times were evaluated. Results: With long-term propagation, we observed significant changes in cell morphology, proliferation, differentiation abilities, and energy metabolism, which were associated with increases in SA-β-gal activity and decreases in telomere length and telomerase activity. Notably, when cultured in 3D, these changes were improved. Conclusions: Our results indicate that 3D culture is able to ameliorate senescence-related changes in ADMSCs.
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