Physcion, a naturally occurring anthraquinone derivative, induces apoptosis and autophagy in human nasopharyngeal carcinoma.

AIM: Physcion is a major bioactive ingredient in the traditional Chinese medicine Radix et Rhizoma Rhei, which has an anthraquinone chemical structure and exhibits a variety of pharmacological activities including laxative, hepatoprotective, anti-inflammatory, anti-microbial and anti-proliferative effects. In this study we investigated the effect of physcion on human nasopharyngeal carcinoma in vitro and in vivo, as well as the mechanisms underlying the anti-tumor action. METHODS: The nasopharyngeal carcinoma cell line CNE2 was treated with physcion, and cell viability was detected using MTT and colony formation assays. Flow cytometry was used to assess the cell cycle arrest, mitochondrial membrane potential loss, apoptosis, autophagy and intracellular ROS generation. Apoptotic cell death was also confirmed by a TUNEL assay. The expression of target or marker molecules was determined using Western blotting. The activity of caspase-3, 8, and 9 was detected with an ELISA kit. A xenograft murine model was used to evaluate the in vivo anti-tumor action of physcion, the mice were administered physcion (10, 20 mg·kg-1·d-1, ip) for 30 d. RESULTS: Treatment with physcion (5, 10, and 20 µmol/L) dose-dependently suppressed the cell viability and colony formation in CNE2 cells. Physcion (10 and 20 µmol/L) dose-dependently blocked cell cycle progression at G1 phase and induced both caspase-dependent apoptosis and autophagy in CNE2 cells. Furthermore, physcion treatment induced excessive ROS generation in CNE2 cells, and subsequently disrupted the miR-27a/ZBTB10 axis, resulting in repression of the transcription factor Sp1 that was involved in physcion-induced apoptosis and autophagy. Moreover, physcion-induced autophagy acted as a pro-apoptotic factor, and possibly contributed to physcion-induced apoptosis. In the xenograft murine model, administration of physcion dose-dependently suppressed the tumor growth without affecting the body weight. Furthermore, the anti-tumor effects of physcion were correlated with downregulation of Sp1 and suppression of miR-27a in the tumor tissues. CONCLUSION: Physcion induces apoptosis and autophagy in human nasopharyngeal carcinoma by targeting Sp1, which was mediated by ROS/miR-27a/ZBTB10 signaling. The results suggest that physcion is a promising candidate for the treatment of human nasopharyngeal carcinoma.

Effects of stellate ganglion block on cardiovascular reaction and heart rate variability in elderly patients during anesthesia induction and endotracheal intubation.

STUDY OBJECTIVE: To investigate the effects of stellate ganglion block (SGB) on cardiovascular response and heart rate (HR) variability in elderly patients during anesthesia induction and endotracheal intubation. DESIGN: A randomized, double-blinded, and placebo-controlled study. SETTING: University-affiliated teaching hospital. PARTICIPANTS: Eighty elderly patients (American Society of Anesthesiologists grades I and II) receiving elective surgery during general anesthesia. INTERVENTIONS: Right stellate ganglion injection (SGB) was performed in all patients using 10 mL of 1% lidocaine or normal saline. MEASUREMENTS: Systolic blood pressure (BP), diastolic BP, HR, and calculated rate pressure product. HR variability at the following time points: conscious status before induction (T0); immediately before intubation (T1); immediately after intubation (T2); and 1, 3, and 5 minutes postintubation (T3, T4, and T5). MAIN RESULTS: No significant differences in BP and HR were observed between the 2 groups. Rate pressure product values significantly increased in the control group compared with baseline and SGB group values. Low-frequency power (LF) and LF/high-frequency power (HF) significantly increased, and HF and normalized units of HF significantly decreased in the control group compared with baseline values. LF, normalized units of LF, and LF/HF in the SGB group significantly decreased compared with those of the control group. CONCLUSION: SGB protects the myocardium and effectively suppresses stress responses during anesthesia induction and tracheal intubation in elderly patients.

Flurbiprofen axetil enhances analgesic effect of fentanyl associated with increase in ß-endorphin levels.

PURPOSE: To examine the analgesic effect of preoperative administration of flurbiprofen axetil and that of postoperative administration of a combination of flurbiprofen axetil and fentanyl, as well as perioperative plasma ß-endorphin (ß-EP) levels in patients undergoing esophagectomy. METHODS: Forty-five patients were randomly divided into three groups: group A: 100 mg flurbiprofen axetil preoperative, 10 µg/kg fentanyl + 10 ml placebo postoperative; group B: 100 mg flurbiprofen axetil preoperative, 10 µg/kg fentanyl + 100 mg flurbiprofen axetil postoperative; group C: 10 ml placebo preoperative, 10 µg/kg fentanyl + 10 ml placebo postoperative. Postoperative analgesia was achieved by intravenous infusion containing flurbiprofen axetil and/or fentanyl at 2.0 ml/h (total volume, 100 ml) using infusion pumps. The ß-EP was measured at preanesthesia (T(1)), the end of surgery (T(2)), 24 h (T(3)), and 48 h (T(4)) after surgery. Visual analog scale scores (VAS) at T3, T4 (at rest), and rescue analgesic tramadol requirement was recorded. RESULTS: The VAS of group B was significantly lower than group A and C (P < 0.01) at T(3) and T(4). The ß-EP levels at T(2)-T(4) in group A did not differ significantly from those at T(1) (P > 0.05); however, the ß-EP levels in group B at T(3)-T(4) increased significantly (P < 0.05), while those in group C increased at T(2) and decreased at T(4) (P < 0.05). The ß-EP levels in group B at T(3) and T(4) were the highest as compared to its levels in groups A and C (P < 0.01). Tramadol consumption in group B was significantly lower than in groups A and C (P < 0.01). CONCLUSION: These results show that flurbiprofen axetil enhances the analgesic effect of fentanyl associated with increase in ß-EP levels.

Quantitative detection of adenosine in urine using silver enhancement of aptamer-gold nanoparticle aggregation and progressive dilution.

We implement the progressive dilution strategy to bring assays based on gold nanoparticles to a quantitative level. This is demonstrated by the detection of adenosine in urine by combining progressive dilution with the silver enhancement of aptamer-gold nanoparticle aggregation, giving good accuracy, high selectivity, and an unlimited dynamic range above LOD.

[Protective effect of ulinastatin on lung injury induced by simultaneous pancreas-kidney transplantation in piglet].

OBJECTIVE: To evaluate the effects of ulinastatin (UTI) on lung injury induced by simultaneous pancreas-kidney transplantation in piglet. METHODS: With reproduction of simultaneous pancreas-kidney transplantation model in piglets, 12 couples of piglets were randomly divided into two groups (n=12). Piglets in UTI group were given a constant infusion of UTI 15 kU x kg(-1) x h(-1) by means of a pump during operation. Control group were treated with constant pumped infusion of 0.9% saline in equal volume. The blood samples were collected to measure the plasma concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) before operation (baseline levels, T0), at the time of re-establishment of circulation with successful an anastomosis of arteries and veins (T1), at 1 hour and 2 hours after re-establishment of circulation (T2 and T3), and at the end of operation (T4). The pathological changes in the lungs were examined. RESULTS: In control group, plasma MDA concentration was significantly increased from T1 till T4 as compared with T0 (all P<0.05), whereas in group UTI it did not change significantly (all P>0.05). In group UTI, SOD activity was significantly increased at T1-2 and T4 as compared with T0 (all P<0.05), whereas in control group it did not change significantly (all P>0.05). The plasma MDA concentration was significantly decreased at T1 and T2, and SOD activity was increased at T2 in group UTI than those in control group (all P<0.05). In control group, plasma TNF-alpha concentration was significantly increased from T2 to T4 as compared with T0 (all P<0.05), whereas it did not change significantly in group UTI (all P>0.05). The plasma IL-8 concentration was significantly decreased at T1-2 and T4 in group UTI compared with those in control group (both P<0.05). CONCLUSION: UTI can inhibit neutrophil aggregation in lungs and expression of harmful inflammatory cytokines, and it reduces production of oxygen free radical, so that it can protect lung tissue from injury induced by simultaneous pancreas-kidney transplantation.

Effects of antidigoxin antiserum on endoxin levels, apoptosis and the expression of Bax and Bcl-2 protein in ischaemia-reperfusion myocardium.

The aim of the present study was to investigate the effects of antidigoxin antiserum (ADA), an endoxin special antagonist, on endoxin levels, apoptosis and the expression of the apoptosis-related protein bcl-2 and bax in myocardial ischaemia-reperfusion (MIR). The left anterior descending coronary artery was subjected to 30 min ischaemia followed by 45 min reperfusion in open-chest anaesthetized rats. The rats were divided randomly into seven groups: a sham-operated group, an MIR group, a vehicle control (normal saline) group, and groups receiving verapamil (5 mg/kg) or ADA (9, 18 and 36 mg/kg). The drugs were injected into rats via the femoral vein before reperfusion was commenced. Myocardial endoxin levels were measured by radioimmunoassay. Apoptotic cells was detected using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling method. The expression of the apoptosis-related proteins bcl-2 and bax was detected by immunohistochemistry and their semiquantification scores were recorded by a computer image analysis system. Myocardial endoxin levels, the number of apoptotic cells and bax protein expression were increased in the MIR group compared with the sham group. Although bcl-2 protein expression was elevated in the MIR group, there was no significant difference between the MIR and sham groups. However, the ratio of bcl-2/bax was significantly decreased in the MIR group. In the group receiving 36 mg/kg ADA, myocardial endoxin levels, the number of apoptotic cells and bax protein expression were significantly decreased; bcl-2 protein expression was enhanced. The bcl-2/bax ratio was increased. The results suggest that ADA inhibited myocardial apoptosis induced by MIR in rats. The mechanisms involved require further investigation, but the present study may suggest that ADA prevents bax upregulation and enhances bcl-2 upregulation by antagonizing the effects of endoxin.