Intramuscular injection of pUDK-HGF is safe, and may provide symptomatic relief for CLI patients. A larger, randomized, double blinded phase II trial will provide more information on safety and efficacy.

BackgroundCritical limb ischemia (CLI) has become a global problem. Less invasive therapy is needed. Hepatocyte growth factor (HGF) is one of the most potent angiogenic protein and the plasmid encoding human hepatocyte growth factor (HGF) is considered to be the most promising gene therapy for CLI. MethodsWe conducted a randomised, double-blind, placebo-controlled trial to assess the e cacy and safety of intramuscular injection of plasmid pUDK-HGF expressing HGF. Pain-at-rest patients and ulcer patients were enrolled as two cohorts and randomized to receive intramuscular injection of placebo or pUDK-HGF. E cacy assessments included pain scale, ulcer size, TBI, ABI, and TcPO 2 over 180 day. Safety analysis was based on the occurrence of adverse events. ResultsIn the pain-at-rest cohort, the proportion of patients with complete pain relief after receiving pUDK-HGF injections was signi cantly higher than that of the placebo group on day 180 (p = 0.0148). More responders with >50% pain reduction were also observed in the pUDK-HGF groups than in the placebo groups (p = 0.0168). In the ulcer cohort of patients, pUDK-HGF treatment tended to be superior to the placebo in the percentage of patients with both complete ulcer healing and >50% ulcer healing. No signi cant differences in the incidence of adverse events or serious adverse events were observed among the groups. ConclusionIntramuscular injection of pUDK-HGF is safe and can signi cantly reduce pain-at-rest and possibly promotes ulcer healing in CLI patients. The mid dose pUDK-HGF (6 mg) was the most e cacious, and is an appropriate dose for phase III clinical trial.

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Multidrug resistance (MDR) of tumor cells is one of the major problems encountered during cancer chemotherapy. In this paper, we isolated eight triterpenoids from Poria cocos and evaluated their effects on reversing MDR of KBV200 cells. Eight triterpenoids increase significantly vincristine-induced cytotoxicity in drug-resistant KBV200 cells at the concentrations of 12.5 µg/mL and 25 µg/mL. Dehydrotumulosic acid showed the best reversal effect: it increased KBV200 apoptosis induced by vincristine and inhibited P-gp function through enhancing the accumulation and retention of fluorescent P-gp substrate rhodamine 123 in KBV200 cells but had no effect on P-gp expression.

The CPSP occurs following various surgical procedures and remains a major clinical problem due to the lack of study on the mechanisms of CPSP. Our findings provide the first evidence that pUDK-HGF attenuates SMIR-induced pain behaviuors through peripheral or central mechanisms. The peripheral analgesic effect of pUDK-HGF is associated with promoting tissue repair and inhibiting inflammatory response; furthermore, pUDK-HGF inhibits activation of spinal glial cells and overexpression of inflammatory mediators in spinal cord. Therefore, naked pUDK-HGF may be a potential therapeutic strategy for treatment of CPSP in clinic.

The results of the present study indicate that pUDK-HGF can reduce cytotoxicity products released from activated glial cells, which may provide a promising therapeutic strategy for treating NP.

A novel glucoside bletilloside A (1) was isolated from the tubers of Bletilla striata, together with seven known compounds (2-8). Their structures were determined on the basis of extensive spectroscopic analyses. All compounds were evaluated for the inhibition on NO production effects in RAW 264.7 macrophage cells, while militarine (4) and dactylorhin A (5) exhibited moderate inhibitory effects.

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