The effects of vitamin C on DDP-induced anemia in rats.

The aim of this study was to investigate the effects of vitamin C on cisplatin (DDP)-induced anemia and explore its possible mechanisms in rats. Adult male Sprague-Dawley rats were randomly divided into six groups: control, vitamin C 50, vitamin C 100, DDP, DDP plus vitamin C 50 and DDP plus vitamin C 100-treated groups. DDP was intravenous injected as a single dose and vitamin C was administered by gavage. Serum erythropoietin (Epo), hemoglobin (Hb) and blood urea nitrogen (BUN) concentration were measured 4 and 14 days after DDP treatment. The changes of renal tissue were examined by light microscope. Administration of DDP to rats induced anemia and nephrotoxicity, characterized with a significant decrease in serum Epo and Hb and increase in BUN concentrations. Pathological examination revealed that DDP caused significant renal damage in rats. Vitamin C administration produced amelioration in biochemical indices of anemia and nephrotoxicity and in histological change when compared to group DDP alone; concurrent administration of vitamin C at doses of 100 mg/kg being more effective. Results from this study indicate that the novel natural antioxidant vitamin C might have protective effect against DDP-induced anemia in rats.

Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets.

BACKGROUND: To discover a compound inhibiting multiple proteins (i.e. polypharmacological targets) is a new paradigm for the complex diseases (e.g. cancers and diabetes). In general, the polypharmacological proteins often share similar local binding environments and motifs. As the exponential growth of the number of protein structures, to find the similar structural binding motifs (pharma-motifs) is an emergency task for drug discovery (e.g. side effects and new uses for old drugs) and protein functions. RESULTS: We have developed a Space-Related Pharmamotifs (called SRPmotif) method to recognize the binding motifs by searching against protein structure database. SRPmotif is able to recognize conserved binding environments containing spatially discontinuous pharma-motifs which are often short conserved peptides with specific physico-chemical properties for protein functions. Among 356 pharma-motifs, 56.5% interacting residues are highly conserved. Experimental results indicate that 81.1% and 92.7% polypharmacological targets of each protein-ligand complex are annotated with same biological process (BP) and molecular function (MF) terms, respectively, based on Gene Ontology (GO). Our experimental results show that the identified pharma-motifs often consist of key residues in functional (active) sites and play the key roles for protein functions. The SRPmotif is available at http://gemdock.life.nctu.edu.tw/SRP/. CONCLUSIONS: SRPmotif is able to identify similar pharma-interfaces and pharma-motifs sharing similar binding environments for polypharmacological targets by rapidly searching against the protein structure database. Pharma-motifs describe the conservations of binding environments for drug discovery and protein functions. Additionally, these pharma-motifs provide the clues for discovering new sequence-based motifs to predict protein functions from protein sequence databases. We believe that SRPmotif is useful for elucidating protein functions and drug discovery.

[Influence of siRNA interfering ß-catenin on tumorigenicity in vivo of K562 cell line].

The aim of this study was to investigate the effects of ß-catenin on the tumorigenicity of K562 cells in vivo. The ß-catenin expression in K562 cells was down-regulated through sequence-specific siRNA, and the treated K562 cells were implanted into BALB/c nude mouse subcutaneously. And the tumor-forming rate and tumor-forming curve (interference group) were observed. Experiments were divided into 3 group: interference group (implanted K562 cells transfected with ß-catenin interfering plasmid DNA), control group (implanted K562 cells transfected with unrelated sequence plasmid DNA) and untreated group (implanted K562 cells transfected without plasmid DNA). The results indicated that the tumor-forming rates of untreated group (n = 9), control group (n = 8) and interference group (n = 9) were 100%, 87.5% and 0% respectively. The tumor-forming rate of interference group was significantly lower than those of the other 2 groups (p < 0.001). Comparison of the tumor-forming curve between 3 groups, showed that in first 2 groups existed tumor-forming and their final tumor volumes were almost the same, but the tumor growth of untreated group was faster than that in control group; while in the interference group there was not tumor-forming. It is concluded that the ß-catenin expression level in K562 cells is down-regulated through the interference of sequence-specific siRNA, thus affecting their tumor-forming potential in vivo.