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Combined radiation-trauma skin injury represents a severe and intractable condition that urgently requires effective therapeutic interventions. In this context, hepatocyte growth factor (HGF), a multifunctional growth factor with regulating cell survival, angiogenesis, anti-inflammation and antioxidation, may be valuable for the treatment of combined radiation-trauma injury. This study investigated the protective effects of a recombinant plasmid encoding human HGF (pHGF) on irradiated human immortalized keratinocytes (HaCaT) cells in vitro , and its capability to promote the healing of combined radiation-trauma injuries in mice. The pHGF radioprotection on irradiated HaCaT cells in vitro was assessed by cell viability, the expression of Nrf2, Bcl-2 and Bax, as well as the secretion of inflammatory cytokines. In vivo therapeutic treatment, the irradiated mice with full-thickness skin wounds received pHGF local injection. The injuries were appraised based on relative wound area, pathology, immunohistochemical detection, terminal deoxynucleotidyl transferase dUTP nick end labelling assay and cytokine content. The transfection of pHGF increased the cell viability and Nrf2 expression in irradiated HaCaT cells. pHGF also significantly upregulated Bcl-2 expression, decreased the Bax/Bcl-2 ratio and inhibited the expression of interleukin-1β and tumor necrosis factor-α in irradiated cells. Local pHGF injection in vivo caused high HGF protein expression and noticeable accelerated healing of combined radiation-trauma injury. Moreover, pHGF administration upregulated Nrf2, vascular endothelial growth factor, Bcl-2 expression, downregulated Bax expression and mitigated inflammatory response. In conclusion, the protective effect of pHGF may be related to inhibiting apoptosis and inflammation involving by upregulating Nrf2. Local pHGF injection distinctly promoted the healing of combined radiation-trauma injury and demonstrates potential as a gene therapy intervention for combined radiation-trauma injury in clinic. [ABSTRACT FROM AUTHOR]

Inflammatory pain and neuropathic pain are major clinical health issues that represent considerable social and economic burden worldwide. In the present study, we investigated the anti-nociceptive efficacy of delivery of human proenkephalin gene by a plasmid DNA vector (pVAX1-PENK) on complete Freund’s adjuvant (CFA) induced inflammatory pain and spared nerve injury (SNI) induced neuropathic pain in mice. Mice were intramuscularly or intrathecally administered pVAX1 or pVAX1-PENK, respectively. Pain thresholds in the pVAX1-PENK treated mice were significantly higher at day 3, then reached a peak at day 7 and lasted until day 28 after gene transfer, and the analgesic effect of pVAX1-PENK was blocked with naloxone hydrochloride. In contrast, pVAX1 treated mice did not significantly improve pain thresholds. These results indicate that peripheral or spinal delivery of a plasmid encoding human proenkephalin gene provides a potential therapeutic strategy for inflammatory pain and neuropathic pain. [ABSTRACT FROM AUTHOR]

We investigated the antinociceptive effect of local intramuscular injection of a plasmid encoding human proenkephalin (pVAX1-hPPE) on postoperative pain in rats. Male Sprague-Dawley rats with incision-induced pain were intramuscularly injected into injured plantaris muscle with empty vector (pVAX1) or pVAX1-hPPE, respectively. Paw mechanical threshold and thermal latency in the 200 μg pVAX1-hPPE treated rats were significantly higher at 6 h and on 1 day, and lasted until day 7 after intramuscular administration, respectively. The analgesic effects were reversed by methylnaltrexone, suggesting that the antinociceptive effect of pVAX1-hPPE was mediated through peripheral opioid receptor pathway. In contrast, incisional or pVAX1-treated rats did not significantly affect pain thresholds. These results demonstrated that single intramuscular injection of pVAX1-hPPE attenuated incision-induced pain in rats, and it is worthy of further study as a potential gene therapy for postoperative pain. [ABSTRACT FROM AUTHOR]