Zhengzhi Wu

Total synthesis of wewakazole B

Wewakazole B is a novel cyclodecapeptide with highly potent cytotoxic activity isolated from a sample of M. producens collected from the Red Sea. It contains nine common and three modified amino acid residues. The first total synthesis of Wewakazole B was successfully achieved on a gram scale, unambiguously confirming its structure. Notable features include the careful choice of amino acid-protecting groups and the construction of three different substituted oxazoles present in this natural product.

Analysis of hippocampal gene expression profile of Alzheimer's disease model rats using genome chip bioinformatics.

In this study, an Alzheimers disease model was established in rats through stereotactic injection of condensed amyloid beta 1–40 into the bilateral hippocampus, and the changes of gene expression profile in the hippocampus of rat models and sham-operated rats were compared by genome expression profiling analysis. Results showed that the expression of 50 genes was significantly up-regulated (fold change ≥ 2), while 21 genes were significantly down-regulated in the hippocampus of Alzheimers disease model rats (fold change ≤ 0.5) compared with the sham-operation group. The differentially expressed genes are involved in many functions, such as brain nerve system development, neuronal differentiation and functional regulation, cellular growth, differentiation and apoptosis, synaptogenesis and plasticity, inflammatory and immune responses, ion channels/transporters, signal transduction, cell material/energy metabolism. Our findings indicate that several genes were abnormally expressed in the metabolic and signal transduction pathways in the hippocampus of amyloid beta 1–40-induced rat model of Alzheimers disease, thereby affecting the hippocampal and brain functions.

Preliminary study on saliva proteomics of different furs in digestive system diseases

Objectives: To explore the material basis for saliva proteome of traditional Chinese medicine furs and biological markers among gastric cancer, chronic gastritis and peptic ulcer. Methods: The experiment included three pathological thin fur, thick fur, stripping fur groups and the normal fur control group. The corresponding peptide mass fingerprinting was acquired by detecting the saliva of subjects using MALDI-TOF-MS technology and Weak Cation Bead (WCX), and to established the classification prediction model. Results: 4 peaks had statistically significant differences (P≪0.05) among 187 differential protein peaks from four groups. The classification prediction model was established with identification rate of 85.31 percent and predictive capability of 39.91 percent. Conclusion: The saliva protein expression diagnosis model was established by using 4 protein peaks of 6447.39Da, 2938.47Da, 1472.34Da, and 1451.77Da as a model to distinguish normal fur from the saliva of different pathological fur.

Preliminary study of salivary proteome on the diagnosis for discrimination of gastric cancer and chronic gastritis

Objective: To investigate and seek the special biomarkers of the salivary protein expression profile for the discrimination diagnosis between gastric cancer and chronic gastritis. Method: The saliva collected were detected by applying WCX magnetic beads and using MALDI-TOF-MS technique. Corresponding peptide mass fingerprint was obtained and differential diagnostic cast was developed. Result: Differences in 77 protein peaks were observed from chronic gastritis and gastric cancer patients. One protein peak among them presented statistical significant difference (p≪0.05). Predictive model for discrimination of gastric cancer and chronic gastritis was developed. Its identification rate was 83.54%, and its capability of predication was 60.23%. Conclusion: The protein expression profile of saliva collected from gastric cancer and chronic gastritis patients was preliminarily obtained. The diagnostic cast for discrimination of the two diseases was classified by the expression of molecular weight 6021.72Da protein.

Analysis on the effect of natural cerebrolysin on gene expression profile of hippocampus in rat AD model by whole genome microarray and bioinformation technologies

Objective: By analyzing the effect of natural cerebrolysin (NC) on gene expression profile of rat hippocampus Alzheimers disease (AD), to explore its molecular genetic pharmacodynamic mechanism of anti-AD. Methods: The experiment included the AD model, sham-operation and NC treated group. The changes of hippocampus gene expression profiles in the above three groups were analyzed by Affymetrix rat whole genome expression profile microarray. Results: Compared to the sham-operation group, the AD model group had 50 up-regulated genes (Fold Change≫2)and 21 down-regulated genes(Fold Change ≪0.5) with significant difference. Compared to the model group, the NC treated group was found to have 5 up-regulated genes and 20 down-regulated genes with significant difference. Conclusion: NC can regulate hippocampal function, and further regulate the brain function of animals in multiple gene target points by a number of ways.

Neuroprotective effect of the Chinese medicine Tiantai No. 1 and its molecular mechanism in the senescence-accelerated mouse prone 8

Tiantai No. 1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No. 1 intragastrically to senescence-accelerated mouse prone 8 (SAMP8) mice (a model of Alzheimers disease) at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimers disease-related proteins in the brain. Tiantai No. 1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No. 1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No. 1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No. 1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No. 1 is neuroprotective in the SAMP8 mouse model of Alzheimers disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.

Analysis of Effects of Natural Cerebrolysin on the Gene Expression Profile of Mesenchymal Stem Cells in Rats by Genome Chip and Bioinformatics

Objective: In order to analyze the effects of Natural Cerebrolycin (NC) on the gene expression profile of Mesenchymal Stem Sells (MSCs), the feasibility of NCs clinical use for Alzheimers Disease(AD)and the mechanism of its gene molecular Pharmacodynamics were studied. Method: The MSCs of rats were isolated and purified by whole bone marrow adherence and adherence screening method, the homology of the cells was analyzed by immunocytochemistry staining technique. The differential expression genes of MSCs treated with NC were analyzed by Affymetric whole genome gene chip analysis method. Result: Rat MSCs of higher purity (more than 90%) was acquired. After MSCs were treated with NC, 45 differential expression genes were displayed, the expressions of 21 genes among them were up-regulated (FC≥2) and the expressions of 24 genes were significantly down-regulated (FC≤-2).These genes included the genes participate in TGFβ / BMPs, Hedgehog, Bmp and Wnt signal transduction pathways that have relations with cell differentiation &development and /or nervous system function, and learning and memorizing functions, the genes of Ras and G protein-coupled receptor signaling pathways that have relations with cell growth and proliferation and apoptosis, and the genes of MAPKKK cascading. Conclusion: NCs anti-AD pharmacodynamic mechanism of molecular genes could have relations with numerous gene expressions of some signal transduction pathways, which participate in regulating nerve cell differentiation and development, nervous system function, functions of learning and memory, and common cell functions of growth, differentiation, proliferation and apoptosis.