DMAG, a novel countermeasure for the treatment of thrombocytopenia.

BACKGROUND: Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. METHODS: In this study, giemsa staining, phalloidin staining, immunofluorescence and flow cytometry were used to identify the effects of 3,3'-di-O-methylellagic acid 4'-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Furthermore, the effects of DMAG on platelet function were evaluated by tail bleeding time, platelet aggregation and platelet adhesion assays. Next, network pharmacology approaches were carried out to identify the targets of DMAG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets. RESULTS: DMAG significantly promoted megakaryocyte differentiation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis, shortened tail bleeding time, strengthened platelet aggregation and adhesion in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K-Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF, p-Akt and PLEK. CONCLUSION: DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia.

Results of hip resurfacing for developmental dysplasia of the hip of Crowe type I and II.

BACKGROUND: Recently, the new generation of metal-on-metal total hip resurfacing arthroplasty is well known for preserving the proximal femoral bone stock, minimizing the risk of postoperative dislocation using large femoral heads, and expecting low wear of metal-on-metal articulation for longer prosthesis survival. It also has the advantage in biomechanical loading in the proximal femur. The osteoarthritis secondary to developmental dysplasia of the hip (DDH) has been the most common reason for total hip arthroplasty. Most of the patients are young and active, who require improved range of motion of the hip besides relief of the pain, even expect to resume the ability to run and jump after the joint arthroplasty, thus to be allowed an active lifestyle. The objective of the current study was to evaluate the early outcome of resurfacing arthroplasty for the mild DDH cases (Crowe type I and II). METHODS: Between September 2005 and May 2007, twenty-one consecutive patients (twenty-six hips) with the diagnosis of osteoarthritis secondary to DDH underwent metal-on-metal resurfacing arthroplasty. The average age at the time of surgery was 46.5 years (range, 37-59 years). Six patients (28.6%) were male and fifteen (71.4%) were female. Clinical and radiographic results were observed. The follow-up was performed at 6 weeks, 3, 6, 9 months and then yearly. RESULTS: All patients were followed for a mean of 18 months (9-29 months). During the follow-up period no complications, such as dislocation of hip joints, infection or femoral neck fracture occurred. The clinical outcomes, as rated with the Harris hip score, improved significantly compared with the preoperative ratings. The mean postoperative Harris hip score was 90.7, compared to 35.5 preoperatively. The radiographic analysis showed that all prostheses were fixed with no radiolucencies. All of the patients who had equal limb lengths preoperatively had equal lengths postoperatively. Of the nine patients with preoperative limb-length discrepancy of 0.8 to 1.2 cm, all regained equal limb length postoperatively. In addition the pain was nearly completely relieved, the range of motion was remarkably improved and no restriction was needed after operation regarding early exercise. CONCLUSIONS: The new generation of metal-on-metal resurfacing arthroplasty may be a reasonable option for DDH of the Crowe types I and II.