The aim of this study was to investigate the effects of resveratrol on endothelial progenitor cell (EPC) activities in vitro and on the mobilization of circulating EPCs, and reendothelialization in balloon-injured aorta of rats. After being isolated, cultured, and characterized, human EPCs were stimulated with resveratrol. We found that a low concentration of resveratrol (1 microM) led to significant enhanced activities of proliferation, migration, and adhesion, as well as promoting endothelial nitric acid synthetase (eNOS) expression in EPCs, whereas a high concentration (60 microM) inhibited the aforementioned functions and eNOS expression. In a rat model of injured aorta, a low dosage of resveratrol (10 mg/kg) increased the amount of EPCs in rat circulation as compared with placebo, whereas the result of a high dosage (50 mg/kg) did not reach statistical difference. In addition, 10 mg/kg of resveratrol both accelerated reendothelialization and inhibited neointimal formation; however, 50 mg/kg only reduced neointimal formation, which was not as effective as the previous one. eNOS expression in injured arteries was potently enhanced in the 10 mg/kg group, but not in the 50 mg/kg group. These findings suggest that a low dosage of resveratrol could markedly raise the proliferative, migrative, and adhesive activities of EPCs and upgrade eNOS expression in vitro as well as increase EPC mobilization, enhance eNOS expression, and accelerate the repair of injured artery; however, a high dosage cannot.
Apoptosis-inducing factor (AIF) represents a caspase-independent apoptotic pathway in the cell, and a mitochondrial localization sequence-truncated AIF (AIFD1-120) can be relocated from the cytoplasm to the nucleus and exhibit a constitutive proapoptotic activity. Here, we generated a chimeric immuno-AIF protein, which comprised an HER2 antibody, a Pseudomonas exotoxin translocation domain and AIFD1-120. Human Jurkat cells transfected with the immuno-AIF gene could express and secrete the chimeric protein, which selectively recognized HER2-overexpressing tumor cells and was endocytosed. Subsequent cleavage of truncated AIF from immuno-AIF and its release from the internalized vesicles resulted in apoptosis of tumor cells. Intramuscular injection of the immuno-AIF gene caused significant suppression of tumors and substantially prolonged mice survival in an HER2-overexpressing xenograft tumor model. Our study demonstrates the feasibility of the immuno-AIF gene as a novel approach to treating cancers that overexpress HER2. Gene Therapy (2006) 13, 313-320.
Thoracic epidural anaesthesia alone is an applied technique of anaesthesia for nephrectomy which has both advantages and limitations. Dexmedetomidine is a highly selective α 2-adrenoreceptor agonist which has both central and peripheral analgesic properties. Forty patients undergoing nephrectomy were enrolled in this clinical trial and allocated randomly to two groups, a control group (C group) and a dexmedetomidine group (D group). The C group received epidural 0.75% levobupivacaine 12 ml with 1 ml of isotonic sodium chloride solution, while the D group received epidural 0.75% levobupivacaine 12 ml with 1 ml (0.5 μg/kg) of dexmedetomidine. Haemodynamic changes, onset time and duration of sensory and motor block, muscle relaxation score, verbal rating score for pain, sedation score and the total postoperative analgesic consumption were evaluated. Sensory blockade duration was longer in the D group than in the C group (P=0.01). The incidence of motor block and the muscle relaxation score were significantly higher in the D group compared with the C group (P=0.01). Compared with the C group, pain scores were significantly lower in the first four postoperative hours in the D group (two hours rest P=0.038; two hours activity P=0.009; four hours rest P=0.044; four hours activity P=0.003). The total amount of flurbiprofen analgesic was significantly lower in the D group compared with the C group (P=0.03). epidural dexmedetomidine 0.5 μg/kg appears to intensify thoracic epidural anaesthesia with levobupivacaine.
The three parameters, rFA, rλ23 and rMD may have predictive value for evaluating hand function outcome in chronic stroke patients.
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