Platelet rich plasma enhanced neuro-regeneration of human dental pulp stem cells in vitro and in rat spinal cord.

Background: Human dental pulp stem cells (hDPSCs) exhibit excellent differentiation potential and are capable of differentiating into several different cellular phenotypes, including neurons. Platelet-rich plasma (PRP) contains numerous growth factors that can stimulate stem cell differentiation. In this study, we investigated the potential stimulatory effects of PRP on neurogenic differentiation and anti-apoptosis of hDPSCs in injured spinal cords. Methods: The unipotential differentiation capacity of hDPSCs was analyzed by cell surface antigen identification and cell cycle analysis. A spinal cord injury rat model composed of 40 Sprague-Dawley (SD) rats was used to facilitate an in vivo study. Rats were divided into four groups: a double-treatment group (receiving both neurogenic-induced hDPSCs and PRP), two single-treatment groups (receiving neurogenic-induced hDPSCs or PRP) and a sham group (receiving normal saline). The Basso, Beattie, Bresnahan Locomotor Rating Scale was subsequently used to evaluate the motor function of the spinal cord. Cell viability and differentiation of hDPSCs in the damaged spinal cords were analyzed and apoptosis of neural cells was evaluated using the terminal uridine nucleotide end labeling (TUNEL) assay. Results: Growth pattern, cell surface marker and cell cycle analyses revealed that hDPSCs have a high degree of multi-directional differentiation potential and can be induced into neurons in vitro. In the rat spinal cord injury model, double-treatment with hDPSC/PRP or single treatment with hDPSCs or PRP significantly improved motor function compared with the sham group (P<0.05). Apoptosis of neural cells was observed to be significantly higher in the sham group compared to any of the treatment groups. Double-treatment with hDPSCs and PRP resulted in the lowest apoptotic rate among the groups analyzed. Conclusions: hDPSCs exhibit differentiation potential and are capable of transforming into neural cells both in vitro and in vivo. Significantly increased inhibition of neuronal apoptosis and improved motor function recovery of the spinal cord were observed following double-treatment with hDPSCs and PRP compared with the single-treatment groups.

Asiatic acid improves high-fat-diet-induced osteoporosis in mice via regulating SIRT1/FOXO1 signaling and inhibiting oxidative stress.

Asiatic acid can attenuate osteoporosis through suppressing adipogenic differentiation and osteoclastic differentiation. Oxidative stress enhances osteoclastic differentiation but represses osteogenic differentiation to promote osteoporosis. However, the role and mechanism of asiatic acid in osteoporosis have not been reported. Firstly, mice were fed with high-fat-diet (HFD) with or without asiatic acid for 16 weeks. Data from an automatic biochemical analyzer showed that HFD induced down-regulation of high-density lipoprotein (HDL) and an increase of serum levels of triglyceride (TG), total cholesterol (TC) and low-density lipoprotein (LDL). However, asiatic acid administration attenuated the decrease of HDL and increase of serum TG, TC and LDL in osteoporotic mice. Secondly, HFD induced high levels of malondialdehyde (MDA) and reactive oxygen species (ROS), low levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in osteoporotic mice. However, the levels of MDA, ROS, SOD and GSH-Px in osteoporotic mice were reversed by asiatic acid administration. (this section is unclear and requires revision) Asiatic acid administration reduced expression of c-telopeptide of type 1 collagen (CTX-1), enhanced alkaline phosphatase (ALP) and procollagen type 1 N-terminal propeptide (P1NP) in HFD-induced osteoporotic mice. (this section is unclear and requires revision) Thirdly, asiatic acid promoted calcium deposition in bone marrow cells and osteogenic differentiation in osteoporotic mice, but decreased ALP in bone marrow cells. Lastly, asiatic acid enhanced SIRT1 and nuclear FOXO1 (Nu-FOXO1) expression, while it reduced Acetyl FOXO1 (Ac-FOXO1) in osteoporotic mice. In conclusion, asiatic acid might inhibit oxidative stress and promote osteogenic differentiation through activating SIRT1/FOXO1 to attenuate HFD-induced osteoporosis in mice.

Changes in bone mineral density and bone metabolic indexes in ankylosing spondylitis mouse model complicated with osteoporosis.

Changes in bone mineral density and bone metabolic indexes in a model of ankylosing spondylitis (AS) mice complicated with osteoporosis (OP) were investigated. BLAB/c mice were used as the subjects. AS was induced using proteoglycan, and OP was induced using tail suspension method. The mice were randomly divided into four groups: AS group, OP group, AS + OP group and negative control group. Changes in bone mineral density, bone strength, serum calcium (Ca), phosphorus, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRACP), in mice of each group were detected and compared. There were statistically significant differences in bone mineral density and bone strength among groups. Compared with the negative control group, bone mineral density and bone strength in the AS, the OP and the AS + OP groups were significantly decreased, and the lowest bone mineral density and bone strength were found in the AS + OP group (P<0.05). There were no significant differences in bone mineral density and bone strength between the AS group and the OP group. Significant differences in serum Ca, ALP and TRACP but not in serum phosphorus were found among groups. Compared with the control group, serum levels of Ca and TRACP in the AS, the OP and the AS + OP groups were significantly increased, while levels of ALP were obviously decreased (P<0.05). Bone destruction in AS mice complicated with osteoarthritis was more serious than that in mice with simple AS.

MiR-204, down-regulated in retinoblastoma, regulates proliferation and invasion of human retinoblastoma cells by targeting CyclinD2 and MMP-9.

Aberrant expression of miR-204 had been frequently reported in cancer studies; however, the mechanism of its function in retinoblastoma remained unknown. Here, we reported that miR-204 was frequently downregulated in retinoblastoma tissues and cell lines. Enforced expression of miR-204 inhibited retinoblastoma cells' proliferation and invasion. In vivo study indicated that restoration of miR-204 inhibited tumor growth. CyclinD2 and MMP-9 were identified as potential targets of miR-204. In addition, a reverse correlation between miR-204 and CyclinD2 or MMP-9 expression was noted in retinoblastoma tissues. Taken together, our results identified a crucial tumor suppressive role of miR-204 in the progression of retinoblastoma.

Comprehensive expression analysis of miRNA in breast cancer at the miRNA and isomiR levels.

Breast cancer (BC) is the main factor that leads cause of cancer death in women worldwide. A class of small non-coding RNAs, microRNAs (miRNAs), has been widely studied in human cancers as crucial regulatory molecule. Recent studies indicate that a series of isomiRs can be yielded from a miRNA locus, and these physiological miRNA isoforms have versatile roles in miRNA biogenesis. Herein, we performed a comprehensive analysis of miRNAs at the miRNA and isomiR levels in BC using next-generation sequencing data from The Cancer Genome Atlas (TCGA). Abnormally expressed miRNA (miR-21, miR-221, miR-155, miR-30e and miR-25) and isomiR profiles could be obtained at the miRNA and isomiR levels, and similar biological roles could be detected. IsomiR expression profiles should be further concerned, and especially isomiRs are actual regulatory molecules in the miRNA-mRNA regulatory networks. The study provides a comprehensive expression analysis at the miRNA and isomiR levels in BC, which indicates biological roles of isomiRs.

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.

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.