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Although the upregulation of Neuropilin-1 (NRP-1) is associated with many solid tumors, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The aim of this study was to investigate the role of NRP-1 in improving treatment and determining the prognosis of pNEN. In this study, the expression of NRP-1 in pNEN tissue samples and pNEN cell line BON1 was analyzed by Western blot, polymerase chain reaction (PCR) and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with small interfering RNAs against NRP-1 or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The expression of NRP-1 in pNEN tissues was markedly increased compared with adjacent normal pancreatic tissues. High NRP-1 expression was strongly correlated with tumor grades (P = .026), lymph node metastasis (P = .025), and tumor-node-metastasis stages (P = .012). Furthermore, NRP-1 downregulation notably inhibited the metastatic capacity of pNEN cells, and STAT3 knockdown was found to downregulate the expression of NRP-1. BON1 cells upregulated NRP-1 expression upon stimulation with IL-6. This was accompanied by activation/phosphorylation of the AKT and STAT3 signaling pathways. Western blot of extracts of human pNENs confirmed increased NRP-1 expression, as well as AKT/STAT3 phosphorylation in tissue of pNENs with elevated expression levels of IL-6. In conclusion, our findings suggest that NRP-1 is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with the IL-6/STAT3 signaling pathway., (Copyright © 2018. Published by Elsevier Inc.)

The poor osseointegration of Ti implant significantly compromise its application in load-bearing bone repair and replacement. Electrically bioactive coating inspirited from heterojunction on Ti implant can benefit osseointegration but cannot avoid the stress shielding effect between bone and implant. To resolve this conflict, hierarchically structured Ti implant with electrically bioactive SnO 2 -TiO 2 bilayered surface has been developed to enhance osseointegration. Benefiting from the electric cue offered by the built-in electrical field of SnO 2 -TiO 2 heterojunction and the topographic cue provided by the hierarchical surface structure to bone regeneration, the osteoblastic function of basic multicellular units around the implant is significantly improved. Because the individual TiO 2 or SnO 2 coating with uniform surface exhibits no electrical bioactivity, the effects of electric and topographic cues to osseointegration have been decoupled via the analysis of in vivo performance for the placed Ti implant with different surfaces. The developed Ti implant shows significantly improved osseointegration with excellent bone-implant contact, improved mineralization of extracellular matrix, and increased push-out force. These results suggest that the synergistic strategy of combing electrical bioactivity with hierarchical surface structure provides a new platform for developing advanced endosseous implants.

Simultaneous targeted cancer imaging, therapy and real-time therapeutic monitoring can prevent over- or undertreatment. This work describes the design of a multifunctional nanomicelle for recognition and precise near-infrared (NIR) cancer therapy. The nanomicelle encapsulates a new pH-activatable fluorescent probe and a robust NIR photosensitizer, R16FP, and is functionalized with a newly screened cancer-specific aptamer for targeting viable cancer cells. The fluorescent probe can light up the lysosomes for real-time imaging. Upon NIR irradiation, R16FP-mediated generation of reactive oxygen species causes lysosomal destruction and subsequently trigger lysosomal cell death. Meanwhile the fluorescent probe can reflect the cellular status and in situ visualize the treatment process. This protocol can provide molecular information for precise therapy and therapeutic monitoring., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)