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This report shows that a nanovector composed of peptide-based nanofibrous hydrogel can condense DNA to result in strong immune responses against HIV. This nanovector can strongly activate both humoral and cellular immune responses to a balanced level rarely reported in previous studies, which is crucial for HIV prevention and therapy. In addition, this nanovector shows good biosafety in vitro and in vivo. Detailed characterizations show that the nanofibrous structure of the hydrogel is critical for the dramatically improved immune responses compared to existing materials. This peptide-based nanofibrous hydrogel shows great potential for efficacious HIV DNA vaccines and can be potentially used for delivering other vaccines and drugs.

The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Numerous mechanisms have been recognized that cause MDR, but one of the most important mechanisms is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, through which the efflux of various anticancer drugs against their concentration gradients is powered by ATP. In recent years, small molecular tyrosine kinase inhibitors (TKIs) have been developed for treatment in various human cancers overexpressing epidermal growth factor receptor (EGFR). At the same time, some TKIs have been shown to be capable of inhibiting ABC transporter-mediated MDR. Dacomitinib (PF-00299804) is a second generation, irreversible TKI, which has shown positive anticancer activities in some preclinical and clinical trials. As many TKIs are substrates or inhibitors of ABC transporters, this study investigates whether dacomitinib could interact with ABC subfamily members that mediate MDR, including ABCB1 (P-gp), ABCG2 (BCRP) and ABCC1 (MRP1). The results showed that dacomitinib at 1.0 μM significantly reversed drug resistance mediated by ABCB1 and ABCG2, but not ABCC1, doing so by antagonizing the drug efflux function in ABCB1- and ABCG2-overexpressing cell lines. The reversal effect on ABCB1-overexpressing cells is more potent than that on ABCG2-overexpressing cells. In addition, dacomitinib at reversal concentration affected neither the protein expression level nor the localization of ABCB1 and ABCG2. Therefore, the mechanisms of this modulating effect are likely to be the following: first, as an inhibitor of ABCB1 or ABCG2 transporters, dacomitinib binds to drug-substrate site in transmembrane domains (TMD) stably in a noncompetitive manner; or second, dacomitinib inhibits ATPase activity and maintains the stability of TMD conformation in a concentration-dependent manner thereby inhibiting the drug efflux function of ABCB1 or ABCG2 transporter. This study provides a useful combinational therapeutic strategy with dacomitinib and substrates of ABCB1 and/or ABCG2 transporters in ABCB1- or ABCG2-overexpressing cancers.

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Ideal tissue-engineering cartilage scaffolds should possess the same nanofibrous structure as the microstructure of native cartilage as well as the same biological function provided by the microenvironment for neocartilage regeneration. In the present study, three-dimensional composite biomimetic scaffolds with different concentration ratios of electrospun gelatin–polycaprolactone (gelatin–PCL) nanofibers and decellularized cartilage extracellular matrix (DCECM) were fabricated. The nanofibers with the biomimetic microarchitecture of native cartilage served as a skeleton with excellent mechanical properties, and the DCECM served as a biological functionalization platform for the induction of cell response and the promotion of cartilage regeneration. Experimental results showed that the composite nanofiber/DCECM (NF/DCECM) scaffolds had stronger mechanical properties and structural stability in wet state compared with those of DCECM scaffolds. In vitro experiments demonstrated that all scaffolds had good biocompatibility, but the chondrocyte proliferation rate of the composite NF/DCECM scaffolds was higher than that of the NF scaffolds. In vitro and in vivo cartilage regeneration results indicated that the DCECM component of the composite scaffolds facilitated early maturation of the cartilage lacuna and the secretion of collagen and glycosaminoglycan. The macroscopic and histological results at 12 weeks postsurgery exhibited that the composite NF/DCECM scaffolds yielded better cartilage repair outcomes than those of the nontreated group and NF scaffolds group. Overall, the present study demonstrated that the structurally and functionally biomimetic NF/DCECM scaffold is a promising tissue engineering scaffold for cartilage regeneration and cartilage defect repair.

We have developed Pharmacogenomics And Cell database (PACdb), a results database that makes available relationships between single nucleotide polymorphisms, gene expression, and cellular sensitivity to various drugs in cell-based models to help determine genetic variants associated with drug response. The current version also supports summary analysis on differentially expressed genes between the HapMap samples of European and African ancestry, as well as queries for summary information of correlations between gene expression and pharmacological phenotypes. At present, data generated on the following anticancer agents are included: carboplatin, cisplatin, etoposide, daunorubicin, and cytarabine (Ara-C). The database is also available to assist in the investigation of the effects of potential confounding variables (e.g. cell proliferation rate) in lymphoblastoid cell lines. PACdb will be regularly updated to include more drugs and new datasets (e.g. baseline microRNA levels). PACdb will be linked into PharmGKB to benefit the next wave of pharmacogenetic and pharmacogenomic discovery.

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