Unveiling the Pharmacological Mechanisms of Eleutheroside E Against Postmenopausal Osteoporosis Through UPLC-Q/TOF-MS-Based Metabolomics.

Postmenopausal osteoporosis (PMOP) is a common metabolic bone disease in postmenopausal women in the Worldwide, and seriously affects the quality of life of middle-aged and elderly women. Therefore, there is an urgent need to discover a highly effective drug for PMOP treatment. In this study, ultra-high performance liquid tandem quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to analyze the urine metabolic profiling and potential biomarkers, the relevant metabolic network of PMOP rats, and further to evaluate the intervention effect of Eleutheroside E (EE) against PMOP. Using multivariate statistical analysis combined with UPLC-Q/TOF-MS, a total of 27 biomarkers were identified, which related with 16 metabolic pathways, mainly involving steroidogenesis, beta oxidation of very long chain fatty acids, glutathione metabolism, carnitine synthesis, estrone metabolism, oxidation of branched chain fatty acids, etc. After treatment of EE, these biomarkers were markedly regulated, mainly involving steroid hormone biosynthesis, arachidonic acid metabolism, primary bile acid biosynthesis, indicating that EE had the therapeutic effect on PMOP. This study identified the potential urine metabolic markers and related metabolic pathways of the PMOP, explained the metabolic effect and pharmacological mechanisms of EE against PMOP, and provided a basis for the pharmacological study of EE.

Deferoxamine enhances neovascularization and accelerates wound healing in diabetic rats via the accumulation of hypoxia-inducible factor-1α.

AIMS: Hypoxia-inducible factor (HIF)-1α plays a pivotal role during the process of wound healing. Previous studies reported that deferoxamine (DFO) could increase HIF-1α stability. This study aimed to investigate the effects of DFO on wound healing in diabetic rats and explore the underlying mechanism both in vivo and in vitro. METHODS: An excisional diabetic wound model was established and the wound healing among vehicle control, DFO and vascular endothelial growth factor (VEGF) treatment groups was evaluated by macroscopy, histology and Western blot analysis. Human umbilical vein endothelial cells (HUVECs) were treated with DFO or HIF-1α siRNA, and then endothelial tube formation, cell proliferation and migration were examined. RESULTS: DFO-treated wounds exhibited accelerated wound healing with enhanced granulation formation and increased re-epithelialization. Compared to the vehicle or VEGF treatment, DFO significantly increased neovascularization through up-regulation of HIF-1α and target genes including VEGF and stromal cell-derived factor-1α (SDF-1α). DFO failed to stimulate the expression of VEGF and SDF-1α in HUVECs depleted of HIF-1α. In addition, DFO promoted the angiogenic-associated processes of endothelial tube formation, cell proliferation and migration in HIF-1α dependent manner. CONCLUSIONS: DFO enhances neovascularization and accelerates diabetic wound healing through the accumulation of HIF-1α and the regulation of endothelial cell function.

[Clinical observation of traumatically-damaged joint after its repair with transplantation of allogenic joint].

OBJECTIVE: To evaluate the long-term function of the traumatically-damaged joint after its repair with transplantation of a fresh or a frozen allogenic joint. METHODS: From March 1977 to September 1993, 13 patients (9 males, 4 females; age, 17-55 years) with traumatically-damaged joints underwent transplantation of the fresh or the frozen allogenic joints. Five patients had 5 damaged metacarpophalangeal joints, 6 patients had 9 damaged interphalangeal joints, and 2 patients had 2 damaged elbow joints. So, the traumatic damage involved 13 patients and 16 joints. All the metacarpophalangeal joints and the interphalangeal joints were injured by machines and the 2 elbow joints were injured by road accidents. The patients were randomly divided into 2 groups: Group A (n=7) and Group B (n= 6). The 7 patients with 8 joints in Group A underwent transplantation of fresh allogenic joints; the 6 patients with 8 joints in Group B underwent transplantation of frozen allogenic joints. The allogenic joint transplants were performed in the period from immediately after the injuries to 6 months after the injuries. The motion ranges of the transplanted joints and the X-ray films were examined after operation, and the immunological examination was performed at 8 weeks after operation. RESULTS: The time for synostosis was 5-8 months in Group A, but 4-6 months in Group B. In Group A, at 2 years after operation the metacarpophalangeal flexion was 30-40 degrees and the interphalangeal flexion was 20-30 degrees; however, at 6 or 7 years after operation the interphalangeal flexion was only 10-20 degrees. The patients undergoing the transplantation with fresh elbow joints had the elbow flexion of 60 degrees and the elbow extension of 0 degrees, and had the forearm pronation of 30 degrees and the forearm supination of 30 degrees. But in Group B, at 2 years after operation the metacarpophalangeal flexion was 60-70 degrees and the interphalangeal flexion was 40-50 degrees; at 6 or 7 years after operation the interphalangeal flexion was still 40-50 degrees. However, the patients undergoing the transplantation with frozen elbow joints had the elbow flexion of 90 degrees and the elbow extension of 0 degrees, and had the forearm pronation of 45 degrees and a forearm supination of 45 degrees. The joint motion ranges, the X-ray findings, and the immunological results in the patients undergoing the transplantation of the frozen allogenic joints were significantly better than those in the patients undergoing the transplantation of fresh allogenic joints. There was a significant difference in the immunological examination between Group A and Group B (IL-2, 21.64 +/- 3.99; CD4/CD8, 3.88 +/- 0.82 vs. IL-2, 16.63 +/- 3.11; CD4/CD8, 2.53 +/- 0.23, P<0. 01). Conclusion Repairing the traumatically-damaged joints with frozen allogenic joints is a better method of regaining the contour, movement, and complex motion of the hands.

[Combined use of autologous micro-morselized bone with bone morphogenetic protein and type I collagen graft in repairing rabbit bone defects].

OBJECTIVE: To study the effect of combined use of autologous micro-morselized bone with bone morphogenetic protein(BMP) and type I collagen graft on the treatment of segmental bone defects. METHODS: The bulk bone of rabbit iliac crest was ground into micro-morselized bone, which was combined with BMP and type I collagen. The model of 1.5 cm bone defect was established in the middle shaft of the radius. Fifty-six rabbits were assigned to four repairing methods: autologous micro-morselized bone graft with BMP and type I collagen, autologous micro-morselized bone graft with type I collagen, autologous micro-morselized bone graft alone, and control group. The defect-repairing capability of each group was assessed by radiographic, histological, bone densitometry and biomechanical studies. RESULTS: X-ray manifested that at the end of 8 weeks after operation, the bone defect treated with autologous micro-morselized bone graft with BMP and type I collagen was repaired completely, and at the end of 12 weeks after operation the bone defect treated with autologous micro-morselized bone and type I collagen was cured completely, but the bone defect treated with autologous micro-morselized alone was completely repaired. No healing was found in the control group. In the bone densitometry detection, the material with BMP exhibited the strongest defect-repairing capability in terms of amount increased and quality of the new bone at the end of 8 weeks and 12 weeks. The group with BMP has the best mechanical strength of all groups at the end of 12 weeks. CONCLUSION: Autologous micro-morselized bone graft with BMP/type I collagen and autologous micro-morselized bone graft with type I collagen prove to be effective in repairing segmental bone defects. The autologous micro-morselized bone combined BMP and type I collagen is an excellent bone repairing material considering the satisfactory osteogenesis, osteo-conduction, and osteo-induction seen in this method.

[The expanded cross-leg flap for repairing the soft tissue defects of the instep].

OBJECTIVE: To explore the clinical application of the expanded cross-leg flap for repairing instep soft tissue defects with bone exposure. METHODS: The expanded cross-leg flap was used to repair instep defects in 10 patients. After flap transferring the donor site was closed directly without skin grafting. RESULTS: Satisfactory results were achieved in all the cases. The flaps survived well. The donor site had less scar and kept good appearance. CONCLUSIONS: The expanded cross-leg flap is a better choice for repairing the soft tissue defects of the instep. It is simple and easy with less trauma to the donor site. After the operation, both the recipient and the donor areas had good appearance.