Effect of Babao Dan on angiogenesis of gastric cancer in vitro by regulating VEGFA/VEGFR2 signaling pathway.

BACKGROUND: To further elucidate the anti-angiogenesis effect of Babao Dan (BBD) in vitro, gastric cancer (GC) cells and human umbilical vein endothelial cells (HUVECs) were used to evaluate the regulation role of BBD by vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway. METHODS: After induced by VEGFA, GC cells (AGS, MGC80-3 and BGC823) were treated by different concentrations of BBD and then were detected cell viability, migration and VEGFA level. And the anti-angiogenesis effect of BBD was evaluated with HUVECs. To furtherly mimic the tumor microenvironment of angiogenesis, VEGFA as an inducer (10 ng/mL) was used to trigger a cascade of angiogenesis of HUVECs in vitro. RESULTS: The viability and migration of GC cells with VEGFA-induced or non-induced and VEGFA levels in GC cells were significantly inhibited by BBD with concentration-dependent manner (P<0.01). BBD significantly inhibited the HUVECs viability with concentration-dependent manner (P<0.01), which was consistent with the inhibitory action on augmentation of cell viability induced by VEGFA (P<0.01). BBD exhibited the similar inhibitory trend on cyto behavioral variability such as wound repairing (P<0.05), migration (P<0.01) and tube formation (P<0.01) and activation effect on cell apoptosis rate (P<0.01) with VEGFA-induced or non-induced. Moreover, BBD notably regulated the levels of VEGFA, VEGFR2, matrix metalloprotein 2 (MMP2) and matrix metalloprotein 9 (MMP9) of HUVECs on present or absent of VEGFA with dose-dependent manner. CONCLUSIONS: BBD inhibited GC growth against VEGFA-induced angiogenesis of HUVECs by VEGFA/VEGFR2 signaling pathway in vitro.

Neuronal EphA4 Regulates OGD/R-Induced Apoptosis by Promoting Alternative Activation of Microglia.

Accumulating evidence indicates that post-injury inflammation characterized by activated microglia contributes much to the neuropathology of ischemic injury. Several studies have demonstrated that microglia exhibit two entirely different functional activation states, referred to as classically activated (M1) and alternatively activated (M2) phenotype. Promoting microglial phenotype to switch from M1 dominant to M2 dominant might be a promising approach for handling ischemic injury. However, the comprehensive mechanism that underlines microglia polarization in ischemic brain remains unclear. Neuronal erythropoietin-producing human hepatocellular carcinoma cell receptor 4 (EphA4), the richest Eph receptor in the central nervous system (CNS), upregulate after ischemia and may have the potential to regulate microglia activation. We hypothesized that modulating EphA4/ephrin signaling could affect ischemic injury through controlling microglia polarization. We therefore knocked down neuronal EphA4 with short hairpin RNA (shRNA) and determined the role of EphA4/ephrin signaling in oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury. We found that EphA4 shRNA treatment attenuated OGD/R-induced apoptosis and microglia proliferation. Neuronal EphA4 knockdown also promoted microglial M2 polarization, which reduced pro-inflammatory mediators and released anti-inflammatory cytokines as well as neurotrophic factors. We further revealed that EphA4 shRNA treatment functioned through RhoA/Rho-associated kinase 2 (ROCK2) signaling, a key mediator of microglia alternative activation. Together, these data suggested that blockage of EphA4/ephrin signaling between neuron and microglia decreased OGD/R-induced injury by promoting alternative activation of microglia via RhoA/ROCK2 signaling.

Experimental Study of Antiatherosclerosis Effects with Hederagenin in Rats.

The research tries to establish Wistar rat's model of atherosclerosis for evaluating the antiatherosclerotic effect of hederagenin and exploring its antiatherosclerosis-related mechanisms. The statistical data have shown that hederagenin exhibits multiple pharmacological activities in the treatment of hyperlipidemia, antiplatelet aggregation, liver protection, and anti-inflammation, indicating that hederagenin may exert a protective effect on vascular walls by improving lipid metabolism disorders and lipid deposition. The results show that hederagenin can correct the imbalance of endothelial function by inhibiting the release of large amounts of iNOS and increasing eNOS contents and inhibits the IKKß/NF-κB signaling pathway to reduce the release of IL-6, IFN-γ, TNF-α, and other inflammatory factors. The experimental results indicated that hederagenin can inhibit or ameliorate the pathological changes associated with AS, displaying an excellent preventive function against AS.

Effects of Kaixin Powder on melatonin receptor expression and (125)I-Mel binding affinity in a rat model of depression.

OBJECTIVE: To explore the effects of Kaixin Powder (, KXP) on melatonin receptor (MR) expression and (125)I-Mel binding affinity in a depression rat model. METHODS: Seventy-two male Wistar rats were divided into six groups: a blank control group, model group, ramelteon group, KXP high-dosage group (HKXP), medium-dosage group (MKXP) and low-dosage group (LKXP). To establish the depression model, all groups except the blank control group were singly housed and exposed to chronic unpredictable mild stress. Weight gain, sucrose consumption and the open-field test were used to evaluate induction of depression. KXP at 260, 130 and 65 mg/(kg•d) was also respectively administered to the rats in the HKXP, MKXP and LKXP groups for 21 days. Ramelteon [0.83 mg/(kg•d)] was given to the positive drug control group. An equivalent volume of physiological saline was given to the blank and model groups. The liquid chip method was used to measure the concentration of plasma melatonin (MT). Mel1a (MT1) and Mel1b (MT2) expression levels were determined by Western blotting. In addition, a radioactive ligand-binding assay was used to analyze the specific binding properties and dynamic characteristics between MR and (125)I-Mel. RESULTS: The results of weight gain, sucrose consumption and the open-field test showed that our model successfully produced depressive symptoms and depressive-like behavior. The concentration of plasma MT in the model group decreased significantly at night but increased in the MKXP group (P<0.05). The HKXP group showed significantly increased expression of MT1 (P<0.05); however, the expression of MT2 in all groups exhibited no significant differences (P>0.05). The maximum binding capacity (B(max)) for specific binding between MR and 125I-Mel in the MKXP group was significantly higher than that in the model group (P<0.05), but no significant differences were found in the equilibrium dissociation constant (K(d)) of each group (P>0.05). CONCLUSIONS: KXP may have a similar effect as ramelteon. KXP improved depressive-like behavior by increasing the concentration of plasma MT and MT1 expression, thereby increasing three B(max) of MR to achieve the desired antidepressant effect.

Daidzein and genistein fail to improve glycemic control and insulin sensitivity in Chinese women with impaired glucose regulation: A double-blind, randomized, placebo-controlled trial.

SCOPE: This randomized, double-blind, and placebo-controlled trial evaluated the effect of isolated daidzein and genistein on glycemic control and insulin sensitivity in 165 Chinese women aged 30-70 with impaired glucose regulation (IGR). METHODS AND RESULTS: Participants were randomly assigned to one of three groups with a daily dose of 10 g of soy protein plus (i) no addition, (ii) 50 mg of daidzein, or (iii) 50 mg of genistein for 24 wk. Fasting glucose (FG), insulin, and glycosylated hemoglobin (HbA1c ), and glucose concentrations at 30, 60, 120, and 180 min and insulin concentrations at 30, 60, and 120 min after an oral 75-g glucose tolerance test were assessed at baseline and at 12 and 24 wk postintervention. a total of 158 and 151 subjects completed the measures at wk 12 and 24, respectively. There were no significant differences in the changes (%) of FG and the 2-h glucose, HbA1c , fasting, and 2-h insulin or the area under the curve of glucose and insulin between the three treatment groups at wk 12 or 24 (all p > 0.05). CONCLUSION: Neither isolated daidzein nor genistein has a significant effect on glycemic control and insulin sensitivity in Chinese women with IGR over a 6-month supplementation period.

[Transbronchoscopic balloon detection and selective bronchial occlusion for intractable pneumothorax].

OBJECTIVE: To evaluate the effect, complications and safety of transbronchoscopic balloon detection (TBD) and selective bronchus occlusion (SBO) for intractable pneumothorax. METHODS: Forty cases of pneumothorax from 5 teaching hospitals in Fujian province were included for this study. TBD was performed in all the 40 cases for whom chest tube drainage had lasted for more than 7days but failed to close the pleura fistulae. Bronchi leading to pleura fistulae (the target bronchus) were detected by balloon-catheter (Olympus B7-2C) through bronchoscope. After the target bronchus was located, SBO procedures were performed. Autologous blood (20 ml to 30 ml) was injected into the target bronchus and followed by thrombin solution (1000 U) through balloon-catheter. In 10 cases, oxygenation and pulse rate were recorded by pulse-oximeter (Healthdyne 920M) during TBD and SBO. Another 10 cases undergoing bronchoscope without performing TBD and SBO served as the controls. Thorax CT, white blood cell count, neutrophil count and body temperature were measured after SBO. RESULTS: Bronchi leading to pleura fistulae were located by TBD in 34 out of the 40 cases. Air leakage was stopped after the first occlusion in 30 cases, but 5 of which underwent a second occlusion because of recurrence in 72 h. Of the 5 cases, air leakage was stopped in 3, and surgery was required in 2. Taken together, 28 of the 34 cases were cured by SBO and 6 failed. There were no statistically differences between the treatment group and the control group in oxygenation changes during TBD and SBO procedures. In 10 cases thorax CT scan was followed up in 7 days after SBO, and no obstructive atelectasis was found. In 20 cases peripheral white blood cell count was followed up 72 hours after SBO. Leukocytosis (> 10.0 x 10(9)/L) was found in 3, in which pulmonary infection was diagnosed, and leukocytosis was present in 2 cases before the procedure. Five patients (5/34) experienced mild to moderate fever, which resolved quickly. CONCLUSION: TBD/SBO are safe and effective procedures for intractable pneumothorax.

[Evaluation of the bleb morphology and the function of post filtration surgery using slit-lamp adapted optical coherence tomography and ultrasound biomicroscopy in glaucoma patients].

OBJECTIVE: To analyze the morphology and the function of subconjunctival filtering bleb in patients with glaucoma by slit-lamp adapted optical coherence tomography (SL-OCT) and ultrasound biomicroscopy (UBM). METHODS: This retrospective study comprised 53 patients with glaucoma filtering surgery from 2002 to 2006. The post-operation blebs in 69 eyes of 53 patients were scanned by a SL-OCT or UBM and categorized by the reference of intrableb morphology. The function of post operation bleb was clarified using Singh's or Yamamoto's criterion. The results of SL-OCT scanning were compared with those of UBM. RESULTS: This is a comparative study. The blebs were classified into four categories according to the images of filtering blebs' by SL-OCT or UBM. SL-OCT had 92.7% (38/41 eyes) sensitivity in predicting a functioning bleb by Singh's standard and 83.3% (20/24 eyes) specificity in predicting a nonfunctioning bleb, whereas, UBM had 66.7% (30/45 eyes) and 75.0% (18/24 eyes) by Yamamoto's criterion, respectively. The sensitivity in predicting a functioning bleb in the SL-OCT group was significantly (P = 0.003, Fisher exact test) different from the UBM group. CONCLUSIONS: Our results suggest that SL-OCT scanning has more sensitivity and specificity than UBM in evaluating the function of filtering bleb. The close relationship between the function and the morphological classification provides an important objective basis in evaluating the outcome of antiglaucomatous surgery.