Identification of Potential Therapeutic Targets of Alzheimer's Disease By Weighted Gene Co-Expression Network Analysis / 中国医学科学杂志(英文版)

Objective Alzheimer's disease (AD) is the most common cause of dementia. The pathophysiology of the disease mostly remains unearthed, thereby challenging drug development for AD. This study aims to screen high throughput gene expression data using weighted co-expression network analysis (WGCNA) to explore the potential therapeutic targets.Methods The dataset of GSE36980 was obtained from the Gene Expression Omnibus (GEO) database. Normalization, quality control, filtration, and soft-threshold calculation were carried out before clustering the co-expressed genes into different modules. Furthermore, the correlation coefficients between the modules and clinical traits were computed to identify the key modules. Gene ontology and pathway enrichment analyses were performed on the key module genes. The STRING database was used to construct the protein-protein interaction (PPI) networks, which were further analyzed by Cytoscape app (MCODE). Finally, validation of hub genes was conducted by external GEO datasets of GSE 1297 and GSE 28146.Results Co-expressed genes were clustered into 27 modules, among which 6 modules were identified as the key module relating to AD occurrence. These key modules are primarily involved in chemical synaptic transmission (GO:0007268), the tricarboxylic acid (TCA) cycle and respiratory electron transport (R-HSA-1428517).

Preliminary establishment of integration of Alzheimer's disease and blood stasis syndrome tree shrew model and evaluation of intervention of Panax notoginseng saponins / 中国中药杂志

To establish the integration of Alzheimer's disease(AD) and blood stasis syndrome tree shrew model. Panax notoginseng saponins (PNS) was used to intervene the model to testify the stability of the model. The level of blood stasis of each group in the tree shrew model was evaluated by analyzing five traditional Chinese medicine(TCM) characterizations, four blood coagulation indexes, plasma nitric oxide (NO) level, plasma superoxide dismutase (SOD) level in each group. Hematoxylin and eosin(HE) staining was used to observe the morphological changes of brain hippocampal neuron cell of each group. Immunohistochemical staining was used to assay the ChAT and SYP levels in brain hippocampus of each group.The blood stasis characterization of the integration of disease and syndrome group was more obvious than the AD group, and that of the drug administration group was lower than that of the integration of disease and syndrome group. Aβ1-42, APP, P-Tau, ChAT and SYP level of AD group were lower than those in the blank group, which were further reduced in the model of integration of disease and syndrome. However, the administration of PNS relieved the reduction, indicating that the AD and blood stasis integration syndrome tree shrew model is stable.

Transesophageal echocardiography guided patent ductus arteriosus occlusion in adults with severe pulmonary hypertension through a parasternal approach.

Between April 2010 and April 2014, 39 consective adult patients (> 18 years) with PDA associated severe pulmonary hypertension underwent transesophageal echocardiography guided patent ductus arteriosus occlusion through a parasternal minimally invasive approach. Among 39 patients, the procedure was successful in 32 cases (82.1%) and failed in 7 cases (17.9%). In the failed cases, 3 cases had a large residual shunt and 4 cases had persistent pulmonary hypertension. The mean minimum miameter of the successfully closed PDAs was 15.2 ± 2.1 mm (range 9 to 24), and the mean diameter of the mushroom-shaped occluder was 17.5 ± 2.5 mm (range 11 to 26). The pulmonary artery pressure decreased significantly after occlusion (P < 0.05), but there were no significant differences in the aortic pressure and blood oxygen saturation before and after occlusion (P > 0.05). Echocardiography performed on the first postoperative day showed decreased volume within the left atrium, left ventricle, and pulmonary artery in 23 cases, decreased volume within the left atrium and left ventricle in 4 cases, and no change in the volume of the atrium and ventricle in 3 cases. A minor residual shunt was observed in 6 cases. The posteroanterior chest X-ray showed improved pulmonary congestion in all cases and significantly reduced cardiothoracic ratio in 25 cases. Patients were followed-up at least for 1 year. No symptoms including palpitation, dyspnoea, or chest tightness were observed. The heart function ranged from NYHA class I to II. A minor residual shunt was observed only in one case. There were varying degrees of decrease in volume within the atrium and ventricle. In conclusion, transesophageal echocardiography guided patent ductus arteriosus occlusion through a parasternal minimally invasive approach is a feasible and effective method for the treatment of PDA in adults with severe pulmonary hypertension.

Effect of PNS on the activity and content of BACE1 in the brain of SAMP8 mice with Alzheimer's disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Panax notoginseng saponin (PNS) on the activity and content of beta-secretase in the brain of senescence accelerated mouse-prone 8 (SAMP8) mice with Alzheimer's disease.</p><p><b>METHODS</b>Totally 32 SAMP8 mice were randomly divided into the normal control group, the high dose PNS group (200 mg/kg), the low dose group (100 mg/kg), and the huperzine A group (0.3 mg/kg), 8 in each group. Equal volume of double distilled water was given to those in the normal control group. All medication was given by gastrogavage, once daily for two successive months. The activity of BACE1 was assayed by direct immunofluorescent method (DIF). The content of BACE1 protein was detected by Western blot.</p><p><b>RESULTS</b>The relative fluorescence units (RFU/microg) was 2.008 +/- 0.031 in the high dose PNS group, 2.221 +/- 0.029 in the low dose PNS group, and 2.267 +/- 0.076 in the huperzine A group, all lower than that in the normal control group (2.403 +/- 0.058; all P < 0.01). The content of BACE1 protein was 0.900 +/- 0.028 in the high dose PNS group, 1.000 +/- 0.032 in the low dose PNS group, and 0.837 +/- 0.080 in the huperzine A group, all lower than that in the normal control group (2.210 +/- 0.074, all P < 0.01).</p><p><b>CONCLUSION</b>PNS higher than 100 mg/kg could decrease the activity of BACE1 and down-regulate the content of BACE1 protein in the brain of SAMP8 mice.</p>

Anti-tumor mechanism of active components from extract of Actinidia rufa root / 中国中药杂志

<p><b>OBJECTIVE</b>To observe effect and mechanism of n-Butanol lysate of alcohol extracts from Actinidia rufa root (monomer of R6,R8).</p><p><b>METHOD</b>Tunel, Wright's stain with Giemsa's stain dyeing, and Hoechst 33258-PI double dyeing assay were used to detect the apoptosis of SGC7901 tumor cells treated with R6, R8. The SGC7901 tumor cells were randomly divided into control group and two treatment groups administered 0.05 g x L(-1) R6, R8, respectively, for 72 h). FCM assay was used to detect the apoptosis. Agarose electrophoresis assay was used to detect DNA strand break of tumor cells and reveal anti-tumor action mechanism.</p><p><b>RESULT</b>The apoptosis percentage of the tumor cell in 24 h, 48 h, 72 h was (17.08 +/- 2.78)% , (29.68 +/- 2.96)%, (52.46 +/- 3.81)%; (14.75 +/- 2.14)%, (27.35 +/- 3.79)%, (45.64 +/- 5.24)%, respectively, for the treatment group, significantly higher than that in the control group (1.94 +/- 1.55)%, (2.78 +/- 1.84)%, (11.8 +/- 2.79)% (P < 0.01) by tunnel assay. Wright's stain with Giemsa's stain dyeing assay, Hoechst 33258-PI and FCM double dyeing assay showed same action. R6 and R8 had the effect of inducing the DNA histogram of tumor cells (P < 0.01).</p><p><b>CONCLUSION</b>The anti-tumor mechanisms may be associated with inducing the injury of DNA and stimulating apoptosis.</p>

Effects of the Panax notoginseng saponins on the level of synaptophysin protein in brain in rat model with lesion of Meynert / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the protective effect of Panax notoginseng saponins (PNS) on the level of synaptophysin ptotein in brain in rat model with Alzheimer's disease (AD).</p><p><b>METHOD</b>The AD rat models were established by intra-peritoneal injection of D-galactose combined with excitatory neurotoxin ibotenic acid injection into bilateral nbM. The activity and content of synaptophysin protein in brain were determined by immunohistochemistry analysis.</p><p><b>RESULT</b>PNS could reduce the lesion of level of synaptophysin protein in brain, as compared with those of model group's rats.</p><p><b>CONCLUSION</b>PNS plays a protective role by reducing down of the level of synaptophysin protein in brain in lesion of AD animal model.</p>

Effect of bushen yizhi recipe on neurotransmitter release in A beta segment neurotoxin induced NG108-15 cellular model of Alzheimer disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Bushen Yizhi Recipe (BSYZR) on neurotransmitter release in A beta segment neurotoxin induced NG108-15 cellular model of Alzheimer disease (AD).</p><p><b>METHODS</b>The levels of choline acetyltransferase (ChAT) activity, synapsin and functional synapse formation rate in the cellular model treated with BSYZR containing serum were determined by Western blot analysis, immunoradiometric assay and electrophysiologic technique.</p><p><b>RESULTS</b>BSYZR containing serum treatment could cause increase of ChAT activity and synapsin level in model cells, as compared with those in normal control model cells treated with non-drug containing serum, it also could regulate the release capacity of transmitter and raise the functional synapse formation.</p><p><b>CONCLUSION</b>BSYZR could reduce the reaction of cell to A beta neurotoxin, indicating that it could be antagonistic to the pathological development of AD by means of raising the neurotransmitter release capacity.</p>