Activity

International efforts to promote predictive toxicology incorporate some form of modeling based on the regularities, insights, and hypotheses gained from analyzing laboratory studies compiled in databases. While there has been a broad commentary on definitions, metadata, and test methodologies, all necessary to establishing data repositories, there has been less on translating the resulting insights into computational models. The recent use of a computational model to support a recommended exposure limit for nanoparticulate silver is an opportunity to examine physiologically based toxicokinetics in terms of data availability, model verification and validation, and regulatory acceptance. The resulting suggestions align with findings from the EU-US Roadmap Nanoinformatics 2030 and the 2018 acceptance of a computational model by the European Food Safety Authority.Background To investigate the anticancer effects of limonoid compounds that were isolated and purified from Xylocarpus granatum fruits on human esophageal cancer (EC) cells. A structure-activity relationship experiment was designed to identify the functional moiety of limonoid compounds identified as being critical for its anticancer activity. Methods Eca109 cells were cultured in RPMI1640 medium and treated with limonoid compounds. Cell proliferation was determined by the MTT assay in vitro. Eca109 cells apoptosis was analyzed by by flow cytometry after being treated with xylogranatin C. The expression of p53, Bax, bcl-2, caspase-3 and GRP78 in Eca109 cells after xylogranatin C treatment was examined by western blot assay. Results Four linonoid compounds strongly inhibited the cellular proliferation of Eca109 cells. Xylogranatin C was the strongest inhibitor, whose inhibitory effect was comparable to that of the well-known chemotherapeutic agent, cisplatin. Furthermore, xylogranatin C might induce Eca109 cell apoptosis through joint effects on multiple pathways, including the death receptor and endoplasmic reticulum pathways. Additionally, xylogranatin C suppressed tumor cell proliferation by upregulating miR-203a expression in Eca109 cells. Conclusions Xylogranatin C induced Eca109 cellular apoptosis and exerted antitumor activity. Xylogranatin C suppressed tumor cell proliferation by upregulating miR-203a expression in Eca109 cells.The reductive coupling of a N-heterocyclic carbene (NHC)-stabilized (dibromo)vinylborane yields a 1,2-divinyldiborene, which, although isoelectronic to a 1,3,5-triene, displays no extended π conjugation due to twisting of the C2B2C2 chain. While this divinyldiborene coordinates to copper(I) and platinum(0) in a η2-B2 and η4-C2B2 fashion, respectively, it undergoes a complex rearrangement to a η4-1,3-diborete upon complexation with nickel(0).Tumour-derived exosomes have been shown to induce pre-metastatic niche formation, favoring metastatic colonization of tumour cells, but the underlying molecular mechanism is still not fully understood. In this study, we showed that exosomes derived from the LLC cells could indeed significantly enhance their intrapulmonary colonization. Circulating LLC-derived exosomes were mainly engulfed by lung fibroblasts and led to the NF-κB signalling activation. Further studies indicated that the exosomal miR-3473b was responsible for that by hindering the NFKB inhibitor delta’s (NFKBID) function. Blocking miR-3473b could reverse the exosome-mediated NF-κB activation of fibroblasts and decrease intrapulmonary colonization of lung tumour cells. Together, this study demonstrated that the miR-3473b in exosomes could mediate the interaction of lung tumour cells and local fibroblasts in metastatic sites and, therefore, enhance the metastasis of lung tumour cells.Simultaneous drug release and monitoring using a single polymeric platform represents a significant advance in the utilization of biomaterials for therapeutic use. Tracking drug release by real-time electrochemical detection using the same platform is a simple way to guide the dosage of the drug, improve the desired therapeutic effect, and reduce the adverse side effects. The platform developed in this work takes advantage of the flexibility and loading capacity of hydrogels, the mechanical strength of microfibers, and the capacity of conducting polymers to detect the redox properties of drugs. The engineered platform is prepared by assembling two spin-coated layers of poly-γ-glutamic acid hydrogel, loaded with poly(3,4-ethylenedioxythiophene) (PEDOT) microparticles, and separated by a electrospun layer of poly-ε-caprolactone microfibers. Loaded PEDOT microparticles are used as reaction nuclei for the polymerization of poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PHMeDOT), that semi-interpenetrate the whole three layered system while forming a dense network of electrical conduction paths. After demonstrating its properties, the platform is loaded with levofloxacin and its release monitored externally by UV-vis spectroscopy and in situ by using the PHMeDOT network. read more In situ real-time electrochemical monitoring of the drug release from the engineered platform holds great promise for the development of multi-functional devices for advanced biomedical applications.To comprehensively evaluate the fermentation performance and microbial community of corn stalks (CS) silage mixed with Neolamarckia cadamba leaves (NCL), CS were ensiled with four levels (0%, 10%, 30% and 50% of fresh weight) of NCL for 1, 7, 14, 30, 60 days in two trials. The results showed that all silages were well preserved with low pH (3.60-3.88) and ammonia nitrogen content (0.08-0.19% DM). The silage samples with NCL displayed lower (P less then 0.05) acetic acid, propionic acid and ammonia nitrogen contents and lactic acid bacteria population during ensiling than control silages (100% CS). The addition of NCL also influenced the distribution of bacterial and fungal communities. Fungal diversity (Shannon’s indices were 5.15-5.48 and 2.85-4.27 in trial 1 and trial 2 respectively) increased while the relative abundances of Lactobacillus, Leuconostocs, Acetobacter and two moulds (Aspergillus and Fusarium) decreased after added NCL. In summary, mixing NCL is a promising effective approach to preserve protein of CS silage and inhibit the growth of undesirable bacteria and mould, thus to improve the forage quality to some extent.