Silencing BLNK protects against interleukin-1ß-induced chondrocyte injury through the NF-κB signaling pathway.

BACKGROUND: Osteoarthritis (OA) is the most common joint disease in the elderly and is characterized by the progressive degeneration of articular cartilage. It is necessary to study the molecular pathology of OA. This study aimed to explore the role and mechanism of BLNK in regulating interleukin-1ß (IL-1ß)-induced chondrocyte injury and OA progression. METHODS: GSE1919 (5 normal samples and 5 OA samples) was downloaded from the Gene Expression Omnibus (GEO) database. The limma package in R software was used to identify differentially expressed genes (DEGs) between control and OA-affected cartilage. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the differentially expressed genes were also performed. Apoptosis was assessed by flow cytometry. An OA rat model was established, and the relative expression of BLNK was assessed by real time quantitative PCR (qRT-PCR) and immunohistochemical staining. The expression of collagen II, MMP9, p65 and p-p65 was measured by Western blot analysis. Moreover, inflammatory factors (TNF-α and IL-18) were assessed by ELISA. The NF-κB inhibitor JSH-23 was used to assess the impact of BLNK on the NF-κB signaling pathway. RESULTS: In total, 1318 DEGs were identified between normal and OA-affected cartilage according to the criteria (P-value <0.05 and |logFC > 1|). These DEGs were mainly enriched in the NF-κB pathway. BLNK was highly expressed in OA cartilage tissue and injured chondrocytes. Silencing BLNK significantly downregulated the IL-1ß-induced apoptosis of chondrocytes. Silencing BLNK partially increased collagen II expression and downregulated MMP13 expression. Moreover, silencing BLNK partially decreased TNF-α and IL-18 expression. BLNK silencing inhibited the activation of NF-κB in OA. Silencing BLNK delayed OA progression through the NF-κB signaling pathway. CONCLUSION: Silencing BLNK delayed OA progression and IL-1ß-induced chondrocyte injury by regulating the NF-κB pathway.

LncRNA RMRP knockdown promotes proliferation and inhibits apoptosis in osteoarthritis chondrocytes by miR-206/CDK9 axis.

The etiology of osteoarthritis (OA) has been discussed widely, but the molecular mechanisms beneath OA aggravation have not yet been investigated in detail. This study focused on the role of lncRNA RMRP (RMRP) on OA progression. We found that the expression of RMRP was significantly increased in cartilage tissues of patients with OA. CCK-8 and colony formation assays showed that RMRP knockdown promoted proliferation of chondrocytes treated with IL-1ß. Flow cytometry and caspase-3 activity analysis indicated that RMRP silence inhibited apoptosis of chondrocytes treated with IL-1ß. Moreover, luciferase reporter, RNA pull-down and RIP assays showed that RMRP competing with miR-206. Additionally, CDK9 acted as a direct target of miR-206. Moreover, rescue assays indicated that miR-206 inhibitor or pcDNA-CDK9 reversed the effects of RMRP suppression on the proliferation and apoptosis of chondrocytes. Taken together, our results indicated that RMRP knockdown could promote proliferation and inhibit apoptosis in OA chondrocytes via the miR-206/CDK9 axis.

Ginsenoside Rg1 Promotes the Migration of Olfactory Ensheathing Cells via the PI3K/Akt Pathway to Repair Rat Spinal Cord Injury.

The aim of this study was to determine the effects of ginsenoside Rg1 on the migration of olfactory ensheathing cells (OECs) in vitro, and its influence on the therapeutic efficacy of OECs transplanted in vivo for the treatment of spinal cord injury (SCI). Primary cultured and purified OECs (prepared from rats) were treated with ginsenoside Rg1. The wound healing test indicated that ginsenoside Rg1 promoted the migration of OECs. Real-time RT-PCR demonstrated that ginsenoside Rg1 upregulated the expression of migration-related factors of OECs, including matrix metalloproteinases-2 (MMP-2), MMP-9, and neural cell adhesion molecule 1 (NCAM1). Moreover, Western blot analysis indicated that ginsenoside Rg1 significantly promoted the migration of OECs via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. An SCI rat model was induced in vivo using a revised Allen's method. The Basso, Beattie, and Bresnahan (BBB) scores and histological analysis demonstrated that OECs, which were treated with ginsenoside Rg1, exhibited significant improvement in SCI compared with both the control group and the OEC group. Thus, ginsenoside Rg1 may represent a novel treatment target for SCI.

Combining mechanisms of black carbon and magnetic minerals in power plant fly ash.

Black carbon (BC), one of the pollutants emitted from fossil fuel combustion, is closely associated with minerals and other hazardous substances. To date, little is known about the mechanisms between BC and magnetic minerals. Accordingly, further investigating the association between magnetic minerals and BC is necessary. In this work, the extraction of BC from fly ash and the magnetic fraction from BC was achieved by flotation and magnetic separation, respectively. The morphology, mineralogical composition, and magnetic properties of BC and magnetic fraction were characterized by FTIR, XRD, SEM-EDS, and vibrating sample magnetometer (VSM). The results show that BC and magnetic minerals have similar mineral compositions, rich in quartz, mullite, magnetite, and hematite. The magnetic minerals have prominent spherical characteristics and are distributed on the surface and inside the pores of BC with irregular honeycomb features. The VSM and XRD analyses show that Fe3O4 is the primary magnetic material. Moreover, large amounts of C, O, and Fe around and on the surface of magnetic spheres were detected by EDS, indicating that the spherical particles may be the structure of BC-coated Fe3O4. Pyrolysis experiments showed that the yield of the magnetic fraction in the pyrolysis product reached 60 %, far exceeding the theoretical yield of 12 % based on 5 % of doped Fe. This further proves that Fe3O4 was combined with a large number of organics during its formation, which may be due to coating and chemical adsorption. Quantum chemical calculations also confirmed this chemical adsorption between Fe3O4 with BC based on density flooding theory, in which adsorption energies ranged from -213.374 KJ/mol to -827.741 KJ/mol.

The deer play in Wuqinxi and four-point hand-knee kneeling positions for training core muscle function and spinal mobility.

The four-point kneeling exercise is a core stabilization exercise that provides the spine with dynamic stability and neuromuscular control. In the traditional Chinese exercise Wuqinxi, deer play is performed in a hand-foot kneeling (HFK) position, which is remarkably similar to the four-point hand-knee kneeling (HKK) position. However, the differences in spinal function promotion between these two positions are poorly understood. The aim of this study was to investigate muscle activation patterns and spinal kinematics during specific core stabilization training to provide evidence for selecting specific exercises. A total of 19 healthy adults were recruited to perform HFK and HKK. The rotation angle of the C7-T4 vertebra and the surface EMG signals of abdominal and lumbar muscles on both sides were collected. The paired t-test showed that the vertebral rotation angles were significantly higher during HKK than HFK, and the intra-group differences mainly occurred at the level of the thoracic vertebra. The muscle activation of both sides of the rectus abdominis and external oblique in HFK was significantly higher than in HKK when the upper limb was lifted (p < 0.05). The activation of the ipsilateral lumbar multifidus and erector spinae muscles was significantly higher during the HKK position than during HFK when the lower limb was lifted (p < 0.05). HFK provided more training for strengthening abdominal muscles, while HKK could be recommended for strengthening lumbar muscles and increasing spine mobility. These findings can be used to help physiotherapists, fitness coaches, and others to select specific core exercises and develop individualized training programs.

The efficacy of coblation nucleoplasty for protrusion of lumbar intervertebral disc at a two-year follow-up.

PURPOSE: The purpose of this study was to evaluate longer-term efficacy over a two-year follow-up of coblation nucleoplasty treatment for protruded lumbar intervertebral disc. METHODS: Forty-two cases of protruded lumbar intervertebral disc treated by coblation nucleoplasty followed-up for two years were analysed. Relief of low back pain, leg pain and numbness after the operation were assessed by visual analogue pain scale (VAS). Function of lower limb and daily living of patients were evaluated by the Oswestry Disability Index (ODI). RESULTS: Operations were performed successfully in all cases. Three patients had recurrence within a week of the procedure. Evaluation of the 42 patients demonstrated significant improvement rate of VAS: defined as 66.2% in back pain, 68.1% in leg pain, and 85.7% in numbness at one-week after the operation; 53.2%, 58.4%, 81.0% at one-year; and 45.5%, 50.7%, 75.0% at two-year follow-up. One week after the operation, obvious amelioration occurred in all the patients, but the tendency decreased. Before operation, the mean value of ODI was 68.2 ± 10.9%. The value at one week was 28.6 ± 8.2%; one-year at 35.8 ± 6.5%; and two-years at 39.4 ± 5.8%. CONCLUSION: Coblation nucleoplasty may have satisfactory clinical outcomes for treatment of protruded lumbar intervertebral disc for as long as two-year follow-up, but longer-term benefit still needs verification.

[Biomechanical effects of different bone cement diffusion patterns after vertebroplasty:finite element analysis].

OBJECTIVE: To investigate the biomechanical effects of different bone cement diffusion patterns in the treatment of osteoporotic vertebral compression fractures. METHODS: One volunteer with L1 osteoporotic vertebral compression fracture was selected, male, aged 68 years old, heighed 172 cm, weighted 60 kg, and healthy before. CT scans were used from T10-L5, CT data was extracted with Mimics software, and Geomagic wrap and Solidworks were used to model, and the three-dimensional finite element model (T12-L2) of preoperative osteoporotic vertebral compression fractures in the thoracolumbar segment was established. Similarly, the situations of bone cement dispersion in vertebroplasty were simulated (the situations of bone cement dispersion had the three kinds, including the bone cement not contacts with upper and lower endplates, the bone cement only contacts with upper endplates, and the bone cement contacts with upper and lower endplates). According to different diffusion situations, five types of loads were applied to the model:upright, upright plus forward flexion, upright plus backward extension, upright plus left bending, upright plus right rotation. Meanwhile, the model was compared with the cementless lumbar spine model, and the deformation and stress distribution of each model under load were recorded and compared. RESULTS: After the establishing the finite element model of osteoporotic vertebral compression fracture in the thoracolumbar segment, it was found that the deformation of three different bone cement distribution models above was not significantly different. In L1 cancellous bone, the Von Mises stress of the cementless lumbar spine group was significantly higher than that of the cemented group. Among the three groups of different bone cement injection situations, the Von Mises stress in the group of bone cement contacts with upper and lower endplates was the lowest, followed by the group of bone cement only contacts with upper endplates, and the highest Von Mises stress was the group that bone cement contacts neither the upper or lower endplates. In the comparison of bone cement stress, the Von Mises stress in the group of bone cement contacts with upper and lower endplates was significantly higher than the other two groups (upright 12.375 MPa, upright plus forward flexion 16.411 MPa, upright plus backward extension 16.801 MPa, upright plus left bending 13.425 MPa, upright plus right rotation 13.014 MPa), and the Von Mises stress in the group of bone cement does not contact with upper and lower endplates was the lowest. CONCLUSION: The bone cement contact with both upper and lower endplates can effectively absorb and transfer the stress level brought by the load, reduce the stress level of cancellous bone, and reduce the possibility of refracture of the operative vertebral body.

Implantation of nanofibrous silk scaffolds seeded with bone marrow stromal cells promotes spinal cord regeneration (6686 words).

Spinal cord injury (SCI) is a common pathology often resulting in permanent loss of sensory, motor, and autonomic function. Numerous studies in which stem cells have been transplanted in biomaterial scaffolds into animals have demonstrated their considerable potential for recovery from SCI. In the present study, a three-dimensional porous silk fibroin (SF) scaffold with a mean pore size of approximately 383 µm and nanofibrous structure was fabricated, the silk scaffold enabling the enhanced attachment and proliferation of bone marrow stromal cells (BMSCs). Investigation of its therapeutic potential was conducted by implantation of the nanofibrous SF scaffold seeded with BMSCs into a transected spinal cord model. Recovery of the damaged spinal cord was significantly improved after 2 months, compared with a non-nanofibrous scaffold, in combination with decreased glial fibrillary acidic protein (GFAP) expression and improved axonal regeneration at the site of injury. Furthermore, elevated Basso-Beattie-Bresnahan (BBB) scores indicated greatly improved hindlimb movement. Together, these results demonstrate that transplantation of neural scaffolds consisting of nanofibrous SF and BMSCs is an attractive strategy for the promotion of functional recovery following SCI.

Ginsenoside Rg1 promotes proliferation and neurotrophin expression of olfactory ensheathing cells.

Transplantation of olfactory ensheathing cells (OECs) is currently considered to be one of the most promising repair strategies for human spinal cord injury. However, the factors that regulate OECs are still poorly understood. Ginsenoside Rg1 (Rg1), the phytosterol from Panax ginseng, is a potent neuroprotective agent that promotes axonal regeneration. The aim of this study is to determine whether Rg1 would influence the biological activity of OECs. Primary cultured OECs from the olfactory bulb of neonatal rats were treated with Rg1 of various concentrations and durations. Using MTT and bromodeoxyuridine assays, we found that Rg1 significantly promoted cell proliferation, with an optimal concentration of 40 mug/ml of Rg1 at 72 h. In addition, RT-PCR and ELISA assays showed that Rg1 could upregulate the mRNA expression and secretion of glial cell-derived neurotrophic factor, brain-derived neurotrophic factor, and nerve growth factor. These results suggest that Rg1 may have a great potential in OEC therapy.

[Local X-irradiation promotes regeneration of spinal cord central nervous system in a rat model].

OBJECTIVE: To evaluate the effect of local X-irradiation on spinal cord injury by using physiology, kinology, electrophysiology and histology method. METHODS: 46 female Sprague-Dawley rats were subjected to spinal cord injury by weight dropping on T(11-12). All animals were divided into 3 groups randomly. One of the animal groups was irradiated with 10 Gy at the lesion site; another was irradiated with 20 Gy, the other without irradiation is regarded as sham-group. The animals were euthanized at different time points at 4 and 12 weeks after irradiation. Spinal cord callus was assessed by using physiology, kinology, and electrophysiology and histology method. RESULTS: In all the groups, the NF at 14 weeks were found higher than that of 6 weeks. Both 10 Gy irradiated and 20 Gy irradiated groups were higher than those of group at each time point (P < 0.05). The MBP decreased at 14 weeks in irradiated groups (P < 0.05), but increased at 14 weeks in sham-group (P < 0.05), the MBP of irradiated groups was lower than that sham-group at 14 weeks (P < 0.05). The GFAP and Nogo-A at 14 weeks were higher than that in 6 weeks in all the groups (P < 0.05), and there was no statistical significance with physiology, kinology, electrophysiology test in all groups. CONCLUSION: A self-repair mechanism exists after SCI, which will last at least 14 weeks. Local irradiation promotes the regeneration of spinal cord system after injury to some extent.

[Diagnosis and operative treatment of far lateral lumbar disc herniation].

OBJECTIVE: To discuss the characteristics and operative selection of far lateral lumbar disc herniation (FLLDH). METHODS: Twenty-three cases of FLLDH, 14 were foraminal, and 9 were extraforaminal lumbar disc herniation. Of the 23 cases, low back pain was observed in 8 cases (31%), severe lower leg pain in 21 cases (91%) and Lasegue sign in 10 cases (43%). CT and MRI showed the protruded disc in and outside of the foramen clearly. Three surgical procedures were performed, including hemilaminotomy with medial facetectomy, facetectomy with pedicle screw fixation and fusion with posteolateral bone grafting, and the transmuscular approaches. RESULTS: Twenty-two cases were followed up for an average of 3.6 years. According to the Macnab criteria, 15 patients achieved excellent results, good 4, fair 3 and poor 0. Excellent and good rate was 86%. CONCLUSIONS: The symptoms and signs of FLLDH mainly result from injury of upper nerve segments with the dominant symptom of severe lower leg pain. CT and MRI appearance are not only sensitive but also specific for the diagnosis of FLLDH. In foraminal lumbar disc herniation, the hemilaminotomy with medial facetectomy is recommended. While in extraforaminal lumbar disc herniation, either facetectomy with pedicle screw fixation and fusion with posterolateral bone grafting or transmuscular approaches for removal of nucleus pulposus can be chosen. Microendoscopic discectomy is a new, safe and efficient method for the disease, however, a skillful microendoscopic technique should be mastered prior.

X-ray therapy promotes structural regeneration after spinal cord injury in a rat model.

OBJECTIVE: This study aims to investigate the therapeutic effects and mechanisms of x-ray treatment on rats following spinal cord injury (SCI). METHODS: Forty-six female Sprague-Dawley rats were subjected to spinal cord injury using the modified Allen weight-drop method. The animals were randomly divided into six groups. Two of the animal groups were irradiated with 10 Gy at the lesion site; another two groups were irradiated with 20 Gy; and the last two groups without irradiation were regarded as the sham group. One of the each of two animal groups was euthanized at different time points at 4 and 12 weeks, respectively, after irradiation. Spinal cord calluses were assessed using kinology and electrophysiology and histology methods. RESULTS: In all of the groups, the neurofilament (NF) counts at 14 weeks were found to be higher than that at 6 weeks after SCI. Both 10-Gy irradiated and 20-Gy irradiated groups were higher than those of the sham group at each time point (P < 0.05). The myelin basic protein (MBP) count decreased at 14 weeks after SCI in the irradiated groups (P < 0.05) but increased at 14 weeks in the sham group (P < 0.05). Furthermore, the MBP count of the irradiated groups was lower than that of the sham group at 14 weeks (P < 0.05). The glial fibrillary acidic protein (GFAP) and Nogo-A counts at 14 weeks were higher than those at 6 weeks in all the groups (P < 0.05), and there was no statistical significance with kinology and electrophysiology tests in all groups. CONCLUSIONS: A self-repair mechanism exists after spinal cord injury, which lasts at least 14 weeks. X-ray therapy promotes the regeneration of the spinal cord system after injury.

TMPRSS4 as an emerging potential poor prognostic factor for solid tumors: A systematic review and meta-analysis.

Recent studies have investigated the potential prognostic value of the transmembrane protease serine 4 (TMPRSS4) in various solid tumors. Yet, the results are inconclusive. Here, we performed this meta-analysis to clarify this issue. Relevant articles were identified by searching PubMed, Web of Science and Embase databases. The primary outcome endpoints were patients' overall survival (OS) and time to tumor progression (TTP). Twelve studies involving 1,955 participants were included. We showed that high TMPRSS4 expression in tumor tissues was significantly associated with patients' poor OS (pooled HR = 2.981, 95% CI = 2.296-3.869, P < 0.001) and short TTP (pooled HR = 2.456, 95% CI = 1.744-3.458, P < 0.001). A subgroup analysis revealed that the association between TMPRSS4 and the outcome endpoints (OS or TTP) was also significant within China region. We conclude that TMPRSS4 overexpression in solid tumors is associated with patients' poor prognosis. TMPRSS4 could be a valuable prognosis biomarker or a promising therapeutic target of solid tumor.

Pedicle screw instrumentation plus augmentation vertebroplasty using calcium sulfate for thoracolumbar burst fractures without neurologic deficits.

OBJECTIVE: To evaluate the efficacy of posterior instrumentation plus vertebroplasty and posterolateral fusion using calcium sulfate for thoracolumbar burst fractures without neurologic deficits. METHODS: Between July 2005 and January 2008, a total of 45 patients who had been diagnosed as having thoracolumbar burst fractures without neurologic deficits were treated with pedicle screw instrumentation plus vertebroplasty using calcium sulfate in our unit. The Cobb angles and loss rates of anterior-middle columns height at different time intervals were measured on lateral radiographs, and the preoperative and postoperative functional outcomes were evaluated using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI). RESULTS: The Cobb angles and loss rates of anterior-middle columns height postoperatively period were restored significantly compared with those noted preoperatively. The angles and heights were well maintained for at least two years using this technique. The mean postoperative VAS (back pain) score was 2.1 ± 0.8, which was significantly better (P < 0.001) than the mean preoperative VAS score 7.9 ± 1.1. The average preoperative ODI was 66.6 ± 8.1% and this had improved significantly to 15.5 ± 4.5% by the latest follow-up (P < 0.001). No instrumentation failure was detected in this study. The calcium sulfate had been absorbed completely by 3-6 months postoperatively. CONCLUSION: Pedicle screw instrumentation plus augmentation vertebroplasty with calcium sulfate is an economic, efficient and reliable technique for treating unstable thoracolumbar fractures without neurologic deficits.

The application of platelet-rich plasma may be a novel treatment for central nervous system diseases.

As a potential biological product, platelet-rich plasma (PRP) has been widely utilized in the areas of oral and maxillofacial reconstruction, bone and soft tissue restoration and wound healing. A recent study reported that the application of PRP on interrupted sciatic nerve could promote remyelinization of peripheral nerve. This renovated a notion that the application of PRP might extend to the nervous system. Most central nervous system (CNS) diseases have a series of common pathological changes in the later period of diseases which induce neurons and glia apoptosis and aggravate neurological dysfunction. It has been demonstrated that the potent restorative function of PRP is mainly based on neurotrophic capacity of preparation rich in growth factors (PRGFs) and scaffolding effect of platelet-rich gel (PRG), all of which could be certified to ameliorate the pathological process of CNS diseases. In view of this, we propose a hypothesis that the application of PRP and its derivatives might provide a novel therapeutic approach for CNS diseases, especially for traumatic brain or spinal cord injury, autoimmune diseases and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.

[Surgical management of traumatic injury of upper cervical spine].

OBJECTIVE: To analyze retrospectively the clinical outcome of surgical management for upper cervical spine injury caused by trauma. METHODS: From January 2005 to March 2007, 16 patients with injury of upper cervical spine were treated by different management. There were 11 males and 5 females with an average age of 44 years ranging from 24 to 75. Of all, 5 cases were the odontoid fracture, 3 were atlas fracture, 5 were Hangman's fracture, 3 were atlanto-axial dislocation. MR imaging of cervical spine showed cervical cord compression and changes of T2 high signal in 5 cases. According to the injury mechanism, the imageological appearance, fracture classification, the methods of treatment were selected. RESULTS: Seven patients received non-operative treatment and nine patients underwent operation. Sixteen patients were followed up for 7 to 34 months (means 10.5 months). All fractures were healing or bone graft fusion and no internal fixation was lossing. There were no injuries of vertebral artery, nerve root or spinal cord. CONCLUSION: CT and MRI are required in the course of diagnosis for the traumatic injury of upper cervical spine. The optimal modus operandi should be choose to retain upper cervical spine, meanwhile, can reserve the cervical movement.

[Analysis of complications associated with internal fixation for lumbar spondylolisthesis].

OBJECTIVE: To evaluate the therapeutic effects of lumbar spondylolisthesis by decompression, instrumentation and posterolateral fusion, and study the causes of the related complications and its method for the prevention. METHODS: One hundred and sixty-five cases with grade I to II spondylolisthesis from February 1991 to May 2007 were retrospectively analyzed. All cases were treated by posterior lumbar canal decompression, reduction with pedicle screw system and fusion with posterolateral bone grafting. Among them,there were 55 male and 110 female with an average age of 53.6 years. Besides, one segment was involved in 161 cases and two segments involved in the rest of them. RESULTS: The complications were divided into either intraoperative postoperative complications. Intraoperative complications were 5 cases (3.0%) there were 4 cases with dura tear and 1 case with nerve root injury. Postoperative complications were 18 cases (10.9%), there were 3 cases with cerebrospinal fluid leakage, 1 case with wound infection, 2 cases with hematoma,5 cases with transient neurological deficits, 1 cases with implant failures and 6 cases with pseudarthrosis formation. CONCLUSION: Good clinical results of lumbar spondylolisthesis can be obtained by posterior reduction and fixation with pedicle screw system. However,operation skills and strict indications play an important role in the prevention of complications.