Neuroprotective Effect of Fructus broussonetiae on APP/PS1 Mice via Upregulation of AKT/ß-Catenin Signaling.

OBJECTIVE: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD). METHODS: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice. To further explore the mechanisms underlying FB's protective effect, PC-12 cells were treated with Aß25-35 in order to establish an in vitro model of AD. RESULTS: FB-treated mice showed improved learning and memory capacity on both the Morris water maze and object recognition tests. RNA-seq of hippocampal tissue from APP/PS1 mice showed that FB had effects on multiple signaling pathways, specifically decreasing cell apoptotic signaling and increasing AKT and ß-catenin signaling. Similarly, FB up-regulated both AKT and ß-catenin signaling in PC-12 cells pre-treated with Aß25-35, in which AKT positively regulated ß-catenin signaling. Further study showed that AKT promoted ß-catenin signaling via enhancing ß-catenin (Ser552) phosphorylation. Moreover, AKT and ß-catenin signaling inhibition both resulted in the attenuated survival of FB-treated cells, indicating the AKT/ß-catenin signaling is a crucial mediator in FB promoted cell survival. CONCLUSIONS: FB exerted neuroprotective effects on hippocampal cells of APP/PS1 mice, as well as improved cell viability in an in vitro model of AD. The protective actions of FB occurred via the upregulation of AKT/ß-catenin signaling.

Protective effects of organic extracts of Alpinia oxyphylla against hydrogen peroxide-induced cytotoxicity in PC12 cells.

Alpinia oxyphylla, a traditional herb, is widely used for its neuroprotective, antioxidant and memory-improving effects. However, the neuroprotective mechanisms of action of its active ingredients are unclear. In this study, we investigated the neuroprotective effects of various organic extracts of Alpinia oxyphylla on PC12 cells exposed to hydrogen peroxide-induced oxidative injury in vitro. Alpinia oxyphylla was extracted three times with 95% ethanol (representing extracts 1-3). The third 95% ethanol extract was dried and resuspended in water, and then extracted successively with petroleum ether, ethyl acetate and n-butanol (representing extracts 4-6). The cell counting kit-8 assay and microscopy were used to evaluate cell viability and observe the morphology of PC12 cells. The protective effect of the three ethanol extracts (at tested concentrations of 50, 100 and 200 µg/mL) against cytotoxicity to PC12 cells increased in a concentration-dependent manner. The ethyl acetate, petroleum ether and n-butanol extracts (each tested at 100, 150 and 200 µg/mL) had neuroprotective effects as well. The optimum effective concentration ranged from 50-200 µg/mL, and the protective effect of the ethyl acetate extract was comparatively robust. These results demonstrate that organic extracts of Alpinia oxyphylla protect PC12 cells against apoptosis induced by hydrogen peroxide. Our findings should help identify the bioactive neuroprotective components in Alpinia oxyphylla.

[Endovascular therapy for traumatic arterial injury].

OBJECTIVE: To explore the clinical efficacies of endovascular therapy for traumatic arterial intima injury, arterial pseudoaneurysm and arteriovenous fistula. METHODS: From October 2009 to December 2011, 24 patients of arterial intima injury, arterial pseudoaneurysm and arteriovenous fistula underwent endovascular therapy including embolism and stent implantation, etc. RESULTS: Among them, 14 patients were punctured directly and another 10 were punctured after the exposure of arteries. The interventions included embolism (n = 3), embolism plus covered stent implantation (n = 2), covered stent implantation (n = 12) and bare stent implantation (n = 7). And the surgical success rate was 100%. After endoluminal treatment, arterial blood flow recovered, arterial pseudoaneurysm shrank, local pain relieved and venous blood pressure decreased. CONCLUSION: As an effective therapy for traumatic arterial intima injury, arterial pseudoaneurysm and arteriovenous fistula, endovascular therapy has minimal trauma, fewer complications and satisfactory outcomes.

[Latest cognition of treatment on deep vein thrombosis of lower extremity].

OBJECTIVE: To explore the effects of surgical procedure combined with the intravascular minimal invasive technique for the treatment of deep vein thrombosis (DVT) of lower extremity. METHODS: At the curse of disease from six hours to ninety days, one hundred and two patients with DVT including one hundred and three lower extremities had received surgical procedure and intravascular minimal invasive treatment. RESULTS: There were not procedure-related morbidities in 102 cases, and symptoms disappeared, all procedures were successful based on angiography. The detecting head for the intravascular ultrasound ablation was entered to inferior vena cava (IVC) in 74 cases (78%), Forgarty catheter was entered to IVC in 21 cases (21%), the stenosis in the confluence of the common iliac vein and IVC was dilated by sacculus rotundus catheter in 89 cases (88%), including 9 patients underwent percutaneous transluminal stenting. One hundred and two patients followed up for twenty months, follow-up by angiography showed no restenosis in 91 cases, restenosis in ilio-femoral vein in 1 cases, and thrombus recontouring in 4 cases, as well as 6 cases died caused by primary disease. CONCLUSION: Surgical procedure combined with the intravascular minimal invasive technique is a safe and effective therapeutic method for DVT.

[Association of p53 gene polymorphism with susceptibility to ovarian cancer].

OBJECTIVE: To investigate the association of p53 codon 72 and p53 intron 3 (PIN3) polymorphism with susceptibility to epithelial ovarian cancer in northern Chinese women. METHODS: p53 codon 72 and PIN3 genotyping was performed by DNA fragments with sequence specific primers among 124 patients with ovarian cancer and 128 healthy control women. RESULTS: The frequency of the Pro and Arg allele among ovarian cancer patients and healthy controls were 53.2%, 46.8% and 46.1%, 53.9%. No significant difference in distribution of allelotype was shown between the two groups (chi(2) = 2.563, P = 0.109). The genotype frequencies of Pro/Pro, Pro/Arg, and Arg/Arg among ovarian cancer and healthy controls were 29.0%, 48.4%, 22.6% and 21.1%, 50.0%, 28.9% respectively. No significant difference was shown between the cases and controls (chi(2) = 2.598, P = 0.273). When the epithelial ovarian cancer patients were grouped according to the pathological characteristics, no significant difference was observed between the patients with serous cystadenocarcinoma or endometrioid carcinoma and the control group or between the two carcinoma groups for p53 codon 72 Pro/Arg (P > 0.05). When the epithelial ovarian cancer patients were divided into two subgroups according to the International Federation of Gynecology and Obstetrics (FIGO) standard, there was a significant difference between the early group (I approximately II) and the late group (III approximately IV) for Arg allelotype and Arg/Arg genotype (chi(2) = 7.494, P = 0.006 and chi(2) = 8.318, P = 0.004). The frequency of A, A'allelotype among ovarian cancer patients and healthy controls was 94.8%, 5.2% and 94.5%, 5.5%, no significant difference was shown between two groups (chi(2) = 0.013, P = 0.91). The genotype frequency of AA, AA', A'A' was not significantly different between the ovarian cancer and healthy controls (chi(2) = 0.301, P = 0.583). There was no significant difference in the frequencies of allelotypes and genotypes between patients with serous systadenocarcinoma and those with endometrioid carcinoma and between patients with ovarian cancers and the control subjects (all P > 0.05). The frequencies of allelotypes and genotypes were not significantly different between early and late ovarian cancers (chi(2) = 0.014, P = 0.906 and chi(2) = 0.137, P = 0.711). CONCLUSIONS: In northern Chinese women, p53 codon 72 Pro/Arg and p53 PIN3 gene polymorphisms are not associated with development of ovarian cancer. Arg/Arg genotype may be used as a stratification marker according to the standards of FIGO for ovarian cancer.