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Spinal cord injury (SCI) is the most commonly seen trauma leading to disability in people worldwide. The purpose of current study was to determine the protective effect of methoxytetrahydro-2H-pyran-2-yl)methyl benzoate (HMPB) on SCI in rat model. TUNEL staining was used to examine apoptotic changes in spinal cord of SCI rats. The ELISA kits were employed to assess inflammatory processes and oxidative factors in the spinal cord tissues. Behavioral changes in SCI rats were assessed using Basso, Beattie, and Bresnahan (BBB) scoring system. Western blotting was used for assessment of proteins. The HMPB treatment of SCI rats reduced apoptotic cell number based on the concentration of dose administered. Treatment of SCI rats with HMPB enhanced BBB score and decreased accumulation of water content in SCI rats significantly. On treatment with HMPB the TNF-α and interleukin-6/1β/18 levels were suppressed in SCI rats. Treatment with HMPB induced excessive release of SOD, CAT, and GSH molecules and decreased overproduction of MDA. The SCI induced upregulation of caspase-3/9 activity was completely alleviated by HMPB at 2 mg/kg dose. The HMPB treatment of SCI rats promoted peroxisome proliferator-activated receptor γ (PPAR-γ) expression, reduced cyclooxygenase (COX)-2 production and increased expression of p-Akt and phosphoinositide 3-kinase (p-PI3K). The study demonstrated that HMPB suppressed apoptosis, raised BBB score and inhibited inflammation in SCI rats. Moreover, activation of PI3K/Akt in the spinal cord tissues of SCI rats was promoted by HMPB. Therefore, HMPB has protective effect on SCI in the rat model.

Background: Mounting researches have established that long-chain non-coding RNA (lncRNA) and microRNA (miRNA) occupy an essential position in osteosarcoma development. The present study attempted to explicate the functional role and mechanism of LINC00485 and miR-361-5p in regulating the osteosarcoma progression.Methods: RT-PCR was employed to measure LINC00485 expression in osteosarcoma tissues and adjacent healthy tissues. Moreover, the correlation between LINC00485 expression and the clinicopathological indexes was analyzed. Further, the LINC00485 low-expressed cell model was constructed, and the CCK8 assay was employed to measure cell proliferation, followed by the flow cytometry in apoptosis testing. Besides, Transwell assay was utilized to detect cell migration and invasion ability, and Western blot examined the alternations of epithelial mesenchymal transition (EMT) marker molecules (E-cadherin and Vimentin). Furthermore, bioinformatics analysis was taken advantage of predicting the downstream molecular targets of LINC00485. RT-PCR and Western blot were carried out respectively to estimate the expression variations of miR-361-5p and Twist1. Dual luciferase activity assay and RNA co-precipitation (RIP) assay were conducted to verify the targeting relationship between LINC00485 and miR-361-5p, miR-361-5p and Twist1.Results: In comparison with normal adjacent tissues, the LINC00485 expression in cancer tissues was profoundly up-regulated. LINC00485 low expression greatly attenuated proliferation, migration, invasion, and EMT in osteosarcoma cells, while enhancing apoptosis. Bioinformatics analysis claimed that miR-361-5p was a sponge miRNA for LINC00485, targeting the Twist1 expression. Further gain- and loss-experiments declared that miR-361-5p limited the osteosarcoma development by inhibiting osteosarcoma cell proliferation, metastasis and promoting apoptosis.Conclusions: LINC00485 acted as an oncogene in the osteosarcoma tumorigenesis by modulating the miR-361-5p/Twist1 axis.

The search for drugs that can facilitate axonal regeneration and elongation following peripheral nerve injury has been an area of increasing interest in recent years. Epothilone B (EpoB) is an FDA-approved antineoplastic agent, which shows the capacity to induce α-tubulin polymerization and to improve the stability of microtubules. Recently, it has been increasingly recognized that EpoB has a regenerative effect in the central nervous system. However, the information currently available regarding the potential therapeutic effect of EpoB on peripheral nerve regeneration is limited. Here, we used a rat sciatic crush injury model system to determine that EpoB strikingly improved axonal regeneration and recovery of function. Also, EpoB (1 nM) did not result in significant apoptosis in Schwann cells (SCs) and showed little effect on their viability either. Interestingly, EpoB (1 nM) significantly enhanced migration in SCs, which was inhibited by autophagy inhibitors 3-methyladenine (3-MA). Since PI3K/Akt signaling has been implicated in regulating autophagy, we further examined the involvement of PI3K/Akt in the process of EpoB-induced SC migration. We found that EpoB (1 nM) significantly inhibited phosphorylation of PI3K and Akt in SCs. Further studies showed that both EpoB-enhanced migration and autophagy were increased/inhibited by inhibition/activation of PI3K/Akt signaling with LY294002 or IGF-1. In conclusion, EpoB can promote axonal regeneration following peripheral nerve injury by enhancing the migration of SCs, with this activity being controlled by PI3K/Akt signaling-mediated autophagy in SCs. This underscores the potential therapeutic value of EpoB in enhancing regeneration and functional recovery in cases of peripheral nerve injury.

BACKGROUND Osteosarcoma, the most common solid malignancy, has high incidence and mortality rates. We constructed a miRNA-based signature that can be used to assess the prognosis of osteosarcoma patients. MATERIAL AND METHODS The miRNA profile was derived from the Gene Expression Omnibus (GEO) website, with matched clinical records. The miRNA-based overall survival (OS)-predicting signature was established by LASSO Cox regression analysis. Receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) analyses were performed to examine the stability and discriminatory ability of the OS-predicting signatures. Pathway enrichment analyses were performed to uncover potential mechanisms. RESULTS Three miRNAs (miR-153, miR-212, and miR-591) independently related to the OS were extracted to build a risk score formula. The ROC curve and K-M analyses revealed good discrimination ability of the OS signature for osteosarcoma patients in both the training cohort (P=0.00015, AUC=0.962) and the validation cohort (P=0.0065, AUC=0.793). As shown in multivariate analysis, the classifier showed favorable predictive accuracy similar to the recurrence status to be an independent risk factor for osteosarcoma. Furthermore, the nomogram showed a synergistic effect by combining the clinicopathological features with our classifier. Also, the enrichment analyses of the target genes may contribute to improved treatment of osteosarcoma. CONCLUSIONS The 3-miRNA-based classifier serves as an effective prognosis-predicting signature for osteosarcoma patients.

Posterior occipitocervical or atlantoaxial fixation and fusion procedures using C2 pedicle or short par or laminar screws instrumentation is widely used to treat patients with atlantoaxial dislocation or instability.

Aims The present study evaluated the functions of Piperlongumine (PL) in osteosarcoma (OS) cell growth and metastasis both in vitro and in vivo. Main methods MTT assay was conducted to test the cytotoxic effects of PL on the human osteoblasts line HFOB1.19 and the human normal chondrocyte line C28/I2T. FITC-Annexin V and propidium iodide (PI) were used to examine cell apoptosis. The migration, invasion and relative epithelial-mesenchymal transition were examined by Transwell assay and Western blotting. Reverse transcription-quantitative PCR (RT-qPCR) was performed to analyze the cytokine signaling 3 (SOCS3) mRNA expression. TargetScan database was used to predict the target of SOCS3. The binding association between miR-30d-5p and SOCS3 in U2OS and MG63 cells was evaluated by the dual-luciferase reporter assay. A xenograft model was constructed to evaluate the effect of PL on OS cell growth in vivo. Key findings The results revealed that PL inhibited the growth, migration, invasion, epithelial-mesenchymal transition, and promoted the apoptosis of OS cells dose-dependently. In addition, PL upregulated the protein levels of suppressor of SOCS3, while it inactivated the JAK2/STAT3 pathway, which was accompanied by a decreased level of microRNA (miR)-30d-5p. Furthermore, SOCS3was confirmed as a novel target of miR-30d-5p. Overexpression of miR-30d-5p not only led to decreased expression of SOCS3, but also dampened the antitumor effect of PL on OS. Significance The present data demonstrated that PL inhibited the progression of OS via downregulation of the SOCS3-mediated JAK2/STAT3 pathway by inhibiting miR-30d-5p.

To explore the effects of salmon calcitonin on the healing process of osteoporotic fractures in ovariectomized rats.We performed this study in The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China, during the period March 2002 to December 2004. We used 120 female adult Wistar rats in this experiment, among which 90 underwent ovariectomy (OVX) and the other 30 had sham-operation. All rats had their left tibias fractured 3 months later. The 90 OVX rats were randomly divided into 3 groups with 30 in each, while the 30 sham-operated rats served as control group. After the fracture the rats had subcutaneous injection of normal saline, salmon calcitonin and estrogen, respectively. X-ray film, histological examination, bone mineral density (BMD) measurement and biomechanics testing were carried out to evaluate the fracture healing.Compared with OVX rats treated with normal saline, the rats with salmon calcitonin had significantly higher BMD values in the left tibia, higher max torque, shear stress of the left tibia 8 weeks after fracture (p0.05), and presented with stronger callus formation, shorter fracture healing time and faster normalization of microstructure of bone trabeculae.Salmon calcitonin can, not only increase BMD in osteoporotic bone, but also enhance the bone biomechanical properties and improve the process of fracture healing in fractured osteoporotic bone.

To observe the degradation of the polylactic glycolate acid (PLGA) microparticles with releasing-slowly vascular endothelial growth factor (VEGF) synthesized by the method of emulsification-diffusion.The method of emulsification-diffusion is to incorporate VEGF into microparticles composed of biodegradable PLGA. The controlled release of microparticles are acquired. The content of the VEGF released slowly from PLGA microparticles in vitro was detected with ELISA at different time.We synthesized 100 releasing-slowly VEGF PLGA microparticles with the size of 0.20-0.33 microm by 5 times. The contents were 62 +/- 11 ng/L, 89 +/- 14 ng/L, and 127 +/- 19 ng/L in the 1st, the 2nd and the 3rd months after degradation, respectively.The PLGA microparticles with releasing-slowly VEGF can be synthesized by the method of emulsification-diffusion.