A novel poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)-PEG-melatonin composite scaffold enhances for inhibiting bone tumor recurrence and enhancing bone regeneration.

Introduction: Postoperative comprehensive treatment has become increasingly important in recent years. This study was to repair tissue defects resulting from the removal of diseased tissue and to eliminate or inhibit the recurrence and metastasis of residual tumors under the condition of reducing the systemic side effects of chemotherapeutic drugs. To address these challenges, multifunctional scaffolds based local drug delivery systems will be a promising solution. Methods: An optimal drug-loaded scaffold material PHBV-mPEG5k (PP5) was prepared, which is biocompatible, hydrophilic and biodegradable. Furthermore, this material showed to promote bone healing, and could be conveniently prepared into porous scaffold by freeze-drying the solution. By means of introducing melatonin (MT) into the porous surfaces, the MT loaded PP5 scaffold with desirable sustained release ability was successfully prepared. The effectiveness of the MT loaded PP5 scaffold in promoting bone repair and anti-tumor properties was evaluated through both in vivo and in vitro experiments. Results and Discussion: The MT loaded PP5 scaffold is able to achieve the desired outcome of bone tissue repair and anti-bone tumor properties. Furthermore, our study demonstrates that the PP5 scaffold was able to enhance the anti-tumor effect of melatonin by improving cellular autophagy, which provided a therapeutic strategy for the comprehensive postoperative treatment of osteosarcoma.

Effects of aspirin on fracture healing in OPF rats.

OBJECTIVES: To study the effect of aspirin on healing process of osteoporotic fracture (OPF) in rats. METHODS: A total of 50 female Wistar rats aged 3 months were randomly divided into observation group and control group, castration method was adopted to establish the osteoporosis (OP) model. After artificial preparing fractures on the midpoint of left femur, fixing gram needle intramedullary, OPF modeling was complete. Aspirin lavage of 33 mg once a day was adopted in observation group after modeling, same amount of normal saline was used in the control as placebo. From each group, selected 5 rats at the 2nd, 4th, 8th and 12th week after modeling to measure the bone mineral density (BMD) and histological examination of the fracture callus, radiology observation was conducted at the 8th and 12th week. Left femur biomechanical measurement was taken at the 12th week. RESULTS: BMD values of observation group at each time point were significantly higher than that of the control group after modeling (P<0.05); Histological observation showed that at the 8th week, the endochondral ossification process of observation group was faster than that of observation group, with fuzzy fracture line in observation group and clear fracture line in observation group; at the 12th week, fracture line disappeared in observation group, fracture line of the control group was fuzzy at the same time; three-point bending load of the left femur in observation group rats was significantly higher than that of control group after 12 weeks (P<0.05). CONCLUSIONS: Aspirin can accelerate the healing of new callus in OPF rats, increase bone density and biomechanics strength, and promote fracture healing of osteoporotic rats.

Effects of local anesthetics on contractions of pregnant and non-pregnant rat myometrium in vitro.

In order to determine whether local anesthetics directly affect the propagation and strength of myometrial contractions, we compared the effects of bupivacaine, ropivacaine, lidocaine and tetracaine on the contractions of myometrium isolated from pregnant and non-pregnant rats. Full-thickness myometrial strips were obtained from 18- to 21-day pregnant and non-pregnant Sprague-Dawley rats and incubated in an organ bath. When spontaneous contractions became regular, strips were exposed to cumulative concentrations of the four local anesthetics ranging from 0.01 to 300 µmol/L and the amplitude and frequency of contraction were recorded. All four compounds caused a concentration-dependent inhibition of the contractility of pregnant and non-pregnant uterine muscle. In pregnant myometrium, the concentration that caused 50% inhibition (IC(50)) was 100 µmol/L for bupivacaine, 157 µmol/L for ropivacaine, > 1000 µmol/L for lidocaine, and 26.3 µmol/L for tetracaine. In non-pregnant myometrium, the IC(50) was 26.9 µmol/L for bupivacaine, 40 µmol/L for ropivacaine, 384 µmol/L for lidocaine, and 7.4 µmol/L for tetracaine. These results suggested that local anesthetics do inhibit myometrial contractions in pregnant and non-pregnant rats in a concentration-dependent manner.

Differentiation of human bone marrow mesenchymal stem cells into neuron-like cells in vitro.

STUDY DESIGN: Responses of human mesenchymal stem cells from bone marrow (hBMSCs) were analyzed under chemical conditions, and then characterization of ion channels was evaluated by whole-cell patch clamp. OBJECTIVE: To explore the possibility of differentiation of human bone marrow-derived mesenchymal stem cells into neuron-like cells in vitro under different conditions. SUMMARY OF BACKGROUND DATA: The generation of mesenchymal stem cells into neuron-like cells has been studied. However, few of these studies characterized functional properties of the differentiated hBMSCs. METHODS: hBMSCs (Passage 2) were expanded and cultured in vitro. After Passage 5 was subcultured, the cells were induced by cytokines and antioxidants. Morphologic observation, immunocytochemistry, Western blot analysis, and patch-clamp techniques were performed to evaluate properties of treated and control groups. RESULTS: The differentiated neuronal cells from hBMSCs not only expressed neuron phenotype and membrane channel protein including Nav1.6, Kv1.2, Kv1.3, and Cav1.2 but also exhibited functional ion currents. Both hBMSCs and differentiated cells expressed Nav1.6, Kv1.2, Kv1.3, and Cav1.2 and voltage-activated potassium currents, including delayed rectifier, noise-like and transient outward currents. However, expression of channel proteins, such as sodium channel Nav1.6 and potassium channels Kv1.2 and Kv1.3, were upregulated. Consistently, their potassium currents were also enhanced in the differentiated cells. CONCLUSION: hBMSCs possess of great potential to differentiate into functional neurons, indicating that hBMSCs may be an ideal cell source in managing a variety of clinical diseases such as spinal cord injury.

Electrophysiological study on differentiation of rat bone marrow stromal stem cells into neuron-like cells in vitro by edaravone.

OBJECTIVE: To explore the electrophysiological properties of differentiation of rat bone marrow-derived stromal stem cells (rBMSCs) to neuron-like cells in vitro by edaravone, a new type of free radical scavenger. METHODS: Stromal stem cells were separated from rat bone marrow with Ficoll-Paque reagent and expanded in different culture medium in vitro. rBMSCs were induced by edaravone containing serum-free L-DMEM. Morphologic observation and Western blot analysis including the expression of Nav1.6, Kv1.2, Kv1.3, Cav1.2 were performed, and whole patch-clamp technique was used. RESULTS: Cyton contraction and long processes were shown in differentiated stromal stem cells. Nav1.6, Kv1.2, Kv1.3 and Cav1.2 were expressed in both differentiated and undifferentiated cells. However, the expression of channel proteins in differentiated cells was up-regulated. Consistently, their resting potential and outward currents were also enhanced in the differentiated cells, which was especially significant in the outward rectifier potassium current. CONCLUSION: In vitro, neuron-like cells derived from rBMSCs, induced by edaravone, possess electrophysiological properties of neurons.

[Effect of Shenqi Fuzheng injection combined with chemotherapy on thirty patients with advanced breast cancer].

OBJECTIVE: To observe the clinical efficacy of Shenqi Fuzheng Injection (SFI) combined with chemotherapy in treating patients with advanced breast cancer. METHODS: Sixty patients were randomly assigned to two groups by digital table, the control group and the treatment group, 30 in each group. All patients were treated with the same CTF regimen of chemotherapy for 21 days as one therapeutic cycle, while those in the treatment group were given SFI additionally in the meanwhite. The therapeutic efficacy was evaluated after 2 cycles of treatment by observing the changes of short-term efficacy, TCM syndrome, quality of life and immune function, as well as the adverse reaction. RESULTS: The total short-term remission rate, the improvement rate of clinical syndrome and quality of life was 50.0%, 70.0% and 76.7% in the treatment group, and 43.3%, 46.7% and 50.0% in the control group, respectively, showing significant difference between the two groups (all P < 0.05). The occurrence of adverse reaction in the treatment group was lower than that in the control group (P < 0.05). The level of CD3+ CD4+ and CD4+/CD8+ ratio increased (P < 0.05) and CD8+ decreased in the treatment group (P < 0.01), while they showed insignificant change in the control group. CONCLUSION: For treatment of advanced breast cancer, SFI can alleviate the bone marrow inhibition caused by chemotherapy, improve clinical symptoms and quality of life and prolong the survival period by regulating cellular immune function of patients, so as to enhance the therapeutic effect of chemotherapy.